Europeans benefit from fast approvals and flexible regulationsThe difference in regulatory climates between the U.S. and Europe is nowhere more evident than in the field of interventional radiology. European radiologists, emboldened by a newly
Europeans benefit from fast approvals and flexible regulations
The difference in regulatory climates between the U.S. and Europe is nowhere more evident than in the field of interventional radiology. European radiologists, emboldened by a newly streamlined regulatory process, are moving forward with clinical applications of new procedures and products that in the U.S. are still mired in the regulatory morass of the Food and Drug Administration. There are signs, however, that U.S. regulatory authorities are beginning to adopt a more European outlook on regulation.
Devices used by interventional radiologists encompass a broad range of products, from fluoroscopy/digital imaging for implants to angiographic catheters, stents, and biopsy needles. Interventional technology is evolving rapidly, and the development of new procedures goes hand in hand with the development of appropriate tools. Due to differences in regulatory approaches, however, the armamentarium available to European interventional radiologists gives them at least a two-year advantage over their transatlantic colleagues. The blame is unequivocally placed on the U.S. regulatory system.
The European market is easier to access in part because of the self-certification process of the Medical Devices Directive (MDD), which came into effect in January 1995. A major component of the MDD is the CE Mark process, which as of January 1996 requires that manufacturers certify that their devices are safe because they satisfy the appropriate provisions of the MDD. The receipt of a CE Mark means that products can be sold and distributed within the European Community without additional national regulation.
Manufacturers are responsible for classifying their own devices, and for determining whether the oversight of a Notified Body is required. Notified Bodies are certified third-party organizations that have been charged with determining whether devices conform to the MDD rules. Where appropriate, CE Marks must be accompanied by the identification number of the responsible Notified Body.
The CE Mark process is less time-consuming and less bureaucratic than the FDA's system, meaning that many interventional radiology devices get to market sooner in Europe, according to Jean-Claude Bonnace, regulatory affairs manager of GE Medical Systems Europe in Buc, France. As a result of the device lag, physicians in the U.S. have to send patients to Europe for endovascular stent grafts. It is also possible to treat abdominal aortic aneurysms in experienced institutions in Europe; technology to unblock veins in the neck is available in Europe but not in the U.S.; and there are over 30 stents on the market in Europe, compared with just four in the U.S.
"It is easier to bring products to the European market, particularly implants," said Frank Le Roi, marketing manager at Boston Scientific International in La Garenne-Colombes, France. "The reasons for this are the FDA and strong patent protection in the U.S."
A 1996 review of European medical device approval times under the MDD showed that products reach the market in as little as a third of the time it takes to gain U.S. approval. Carried out by Medical Technology Consultants Europe (now Quintiles-MTC), the study found that breakthrough medical devices were approved in Europe within 80 to 120 days, provided that the manufacturer had passed a European Union (EU) facility inspection. Similar devices took an average of 773 days to gain FDA approval. Although improvements have been made by the FDA in the last year-the average review time for 510(k)s was 110 days in fiscal 1996, and nine premarket approvals (PMAs) were granted in under a year-there seems little likelihood of closing the gap completely.
For devices that require clinical trials, the process is even more complex in the U.S. The FDA requires more than one study, whereas one may be all that is required in Europe. There are differences in the regulatory authorities' approach to clinical trial requirements, too: In general, the end results are the main concern in the EU, while the FDA has much more involvement in the study protocol and report. FDA reviewers take a far more detailed look at the data than do the less experienced European Notified Bodies. In addition, in the U.S., manufacturers have to prove that their device is equal to or better than existing products, but in Europe they need prove only that it is safe, according to Jesper Thyregod, marketing manager for William Cook Europe in Bjaeverksov, Denmark.
Some people believe, however, that the U.S. system is not altogether detrimental, and there is an undercurrent of concern among interventional radiologists that European requirements may not be providing the degree of clinical evaluation they would like to see before products are placed on the market. Some interventional radiologists feel that the MDD focuses more on manufacturers' compliance with standards than on clinical safety, and that CE-marked devices are being sold before they are clinically proven. The CE marking means that the materials are safe, but it does not prove that a device will produce the desired clinical results, according to one leading U.K. interventional radiologist.
Although FDA requirements are considered overly stringent by manufacturers, Dr. Hervé Rousseau, an interventional radiologist in Toulouse, France, believes that more of this kind of evaluation is needed in Europe.
"The CE marking is organized more for companies than for patients. It affects few doctors and there are few data for clinical evaluation," Rousseau said. "Up to now the law in Europe has been less restrictive than the FDA, but this is changing with the CE marking. We need more evaluation along the lines of the U.S. FDA. I hope this will happen."
R&D slowdown? Has the more restrictive regulatory environment in the U.S. impeded the development of new products? Peter Winzeler of Schneider in Bülach, Switzerland, doesn't think so. Companies work with customers independent of the regulatory situation. Product development involves a range of factors-technical feasibility, patents, marketing-in addition to regulatory requirements. Whether the regulatory process takes three months or three years will influence development decisions, but it will not be a question of whether to proceed, he said.
Europe is often used as a test market for interventional devices because products reach customers more quickly, but the major companies are increasingly involved in globalization and cannot shift their R&D investment from the U.S. Schneider is among a growing number of companies viewing product development from a global perspective.
Most of GEMS' products are available to interventional radiologists in both Europe and the U.S. Bonnace believes that the U.S. is still a good market in which to conduct R&D, and that it even has some advantages over Europe: It is a united country with uniform regulations and one language, unlike Europe which, apart from linguistic differences, contains different attitudes among practitioners and national regulatory variations.
National differences in registration, labeling, clinical trials, and vigilance requirements mean that manufacturers are still having to contend with a myriad of conditions in Europe. For example, technology to repair aortic aneurysms is available in some European countries but not in France, where it has to undergo a one-year study (due to be completed by the end of 1997) before it can be marketed. There are large differences within Europe, Rousseau said.
Attempts to reconcile EU and U.S. device regulations are proving tough. European firms are not happy with the FDA and wish to achieve equivalency for good manufacturing practices and 510(k) requirements, Bonnace said. The FDA's apparent unwillingness to change is showing some sign of weakening, however, and progress is also being made in mutual acceptance of quality standards. The U.S. and EU have reached a Mutual Recognition Agreement that will obviate quality system inspections on both sides of the Atlantic (SCAN 6/25/97).
Although any further changes to U.S. laws regulating devices will require congressional intervention, Dr. Bruce Burlington, the director of the FDA's Center for Devices and Radiological Health, has started to hint at a shift toward the European approach. Thus, there is a glimmer of hope that U.S. regulations could more closely match the requirements of Europe's MDD, 1at least in certain areas.