On the morning of 1 May 2004, 75 million Europeans awoke as new citizens of the European Union (EU). The EU expanded to incorporate ten new member states: Estonia, Lithuania, Latvia,Poland, the Czech Republic, the Slovak Republic, Hungary, Slovenia, Malta and the Republic of Cyprus. The new 25-member EU now encompasses 455 million people — about 40% more than the US and Canada combined.
For drug makers, the expanded union presents many opportunities, says David Redfern, Senior Vice President for Central Europe at GlaxoSmithKline. Five to ten years from now, Redfern predicts, the economies of many former Eastern Bloc countries will have picked up. So will, he hopes, the percentage of national income spent on health care, which in some countries falls behind similar expenditures in the west.
In addition, new EU rules will extend data exclusivity protection from six to ten years in new member states, as well as a number of old ones, giving some brand products longer shelf lives. Taken together, Redfern says, things look markedly positive, which is why GSK is investing in manufacturing facilities in central Europe.
But the expanded union also poses many challenges. EU consumers now speak twenty languages instead of eleven, doubling the need for costly translations of all marketing material. And with drug prices ranging among member states, the potential for parallel trade looms large.
The main issue to be resolved is the sometimes lengthy and obscure ways of getting newly developed drugs to consumers. There are still two routes for approval: through the oldfashioned country-by-country route which still exists for extending national approvals or getting approval in just a few EU countries, and through a centralized procedure with the London-based European Agency for the Evaluation of Medicinal Products (EMEA), which provides approval in all member states simultaneously.
Extending market approval from one EU country to others often leads to authorities squabbling at national levels rather than facilitating speedy follow-up approvals, a situation that is unlikely to improve with ten more member states joining the fray.
The centralized procedure bypasses this. Average approval times are similar to FDA–around 17 months–but many individual drugs take longer to be approved in the EU because the EMEA cannot give priority review treatment. For example, the FDAs priority review of bortezomib (Velcade;Millennium) led to approval and launch within four months after submission in January 2003. However it took a year before EMEA voiced a positive opinion, and at the time of writing approval by the European Commission is still pending.
So, last year the old EU member states agreed to overhaul drug approval legislation, which will come into effect shortly after the EU expansion. “The changes constitute subtle but important shifts towards a more central role for the EMEA,” says Martin Harvey Allchurch, head of EMEA’s executive support office.
Some things will change immediately. Besides renaming the bureau to European Medicines Agency (still EMEA), its governing and scientific advisory boards will be trimmed from two to one member per country. The committee evaluating human drugs, formerly called Committee for Proprietary Medicinal Products (CPMP), will be known as Committee for Human Medicinal Products (CHMP).
Other changes will take effect in November 2005, when all 25 member states have updated their national laws. Part of the shift will occur with the decentralized procedure. At present, this route is infamous for delays and protracted arguments between member states. The new rules order the EMEA to solve disagreements in a new ‘Coordination Group’, in which all member states are represented. Also, all relevant countries will be kept up to date during evaluation in the first member state, cutting months of delays for secondary registrations.
The rest of the changes focus on the centralized procedure, at present mandated mainly for biotech drugs. As of next year, any drug for cancer, HIV, diabetes or neurodegenerative and rare diseases will have to pass through this procedure.
Like the FDA, EMEA plans to put drugs with a high unmet clinical need on a ‘fast track’ procedure, bypassing less urgent applications and cutting an average of 60 from the 210 active days decisions can take. (EMEA refers to approvals both in terms of ‘total review time’ and ‘active review time’.) Drugs expected to have great public health implications will be eligible for pre-approval release for ‘compassionate use’ or can be approved on the condition that more safety data will be collected.
Greater emphasis will also be placed on transparency. Doctors and patients will have seats in the EMEA governing board (at present the FDA has patients only in some advisory committees). Scientific committees at the EMEA will publish all decisions and relevant company data, even when the drug is rejected or the application withdrawn. Information like this can be relevant for patients taking drugs in clinical trials or programmes for compassionate use, says Harvey.
So, will this bigger, modernized EU convince companies to register new drugs in Europe before trying their luck in the United States?
It’s unlikely, says Redfern, as better approval procedures, although welcome, are just one part of the struggle to get drugs to patients in Europe. It has been getting harder and harder, he says, to get products accepted for reimbursement by health care systems in various countries. “We have seen cases where getting drugs to patients in one country took five years longer than it took in others,whereas in some countries they never reached them at all,” says Redfern. “Sometimes there are scientific reasons. But sometimes it’s just to keep health care costs down.”
Frits Lekkerkerker, chairman of the Medical Evaluation Board in The Netherlands and alternate member of the new CHMP, agrees. Although differences are subtle, Lekkerkerker says, “the EMEA still is somewhat more conservative with drugs that look promising but lack scientifically convincing proof.” But, more importantly, says Lekkerkerker, as long as the US market yields bigger profits, the FDA will continue to be many companies’ first choice.