An MD&DI April 1999 Column
An executive specializing in international regulatory affairs assesses the current movement toward globalization and identifies key areas requiring the most urgent action.
In both the drug and device industries, we are seeing significant movement toward bringing international regulatory systems in line with one another. But many Americans continue to wonder whether we, as industry members and as a country, are ready to move along this road, and if so, how fast and how far should we go? What are the various tools we can use to reach the desired destination, and what is the role of each? Does any of this diminish the role of FDA in protecting the health of the American public?
My thoughts on these questions reflect the perspective of a company that operates in more than 120 countries, producing implantable, critical-care devices that are subject to the most stringent controls of a wide range of regulatory systems. They also reflect my observations regarding what is happening around the world in the broader context of healthcare delivery.
The first question that must be answered is whether there is solid justification for moving toward harmonization. For an answer, we must take stock of today's medical environment. First of all, medical technology manufacturers such as Medtronic are now developing products to meet the demands of patients and the medical community in a global medical marketplace. In addition, in all countries, the pressure to control healthcare costs is growing. Because the proliferation of divergent regulatory systems significantly slows the dissemination of new technology across borders and increases total healthcare costs, the world is naturally progressing toward globalized regulatory requirements.
If harmonization of medical device regulation is occurring naturally, the real issue thus becomes a question of where that process should be leading us. The end result must be able to keep unsafe medical devices off the market. But this doesn't mean that a system like FDA is needed. In fact, FDA-like regulatory systems are inappropriate and impossible in most countries, especially those in Asia. All developed nations are rapidly moving toward the same level of sophistication when it comes to the evaluation of medical devices, be they Class I, II, or III. The European Union (EU) has created a regulatory mechanism that ensures the highest level of safety for patients, while quickly moving beneficial products to the market. The EU has already established a very credible review system for medical devices through efforts such as basing the process on quality system standards, using the world-class, globally recognized ISO 9000 series of standards.
In fact, as countries update their regulatory procedures, most are following the lead of Europe. The EU is aggressively pursuing mutual recognition agreements (MRAs) with many non-EU partners, including Switzerland, Canada, Australia, and some Asian countries. Even without an MRA with the EU, some Asian countries, notably China, are unilaterally adopting an EU-style regulatory approach. The United States cannot remain insular; the world is moving ahead, and we cannot afford to be left behind.
I want to be clear that I believe we need a strong FDA that has the confidence of the American people. But I do not believe that globalization of medical device regulationincluding both a move toward harmonization and the achievement of device MRAsis in conflict with protecting the sovereignty of the United States or the ability of FDA to carry out its mission. We cannot reach our goal overnight, but we need to keep progressing, and FDA must continue to play an active role in the process. There are places we can start right now, and there are other areas that need enhanced industry support.
I'd like to suggest five such areas in which global harmonization efforts should be focused. They are:
- Moving ahead quickly regarding an MRA with the EU, particularly on quality systems.
- The acceptance of a universal data set for clinical trials.
- The recognition of international performance standards.
- Steady progress toward an MRA with the EU on product approvals done according to a manufacturer's own country's requirements by accredited third parties, starting with 510(k) devices.
- The acceptance by regulatory authorities in Asia of a common dossier.
A brief review of these five areas will perhaps offer some justification for my thoughts. First, with regard to reaching an MRA for quality system standards, FDA deserves significant credit for progress made in this area. The agency's new quality system regulation (QSR), which replaces good manufacturing practices (GMPs), is nearly identical to ISO 13485/13488. Both are based on a quality system approach, a concept that did not exist when GMPs were first developed, and both ensure a higher degree of product quality than ever existed before. FDA's new QSIT inspection program is another positive development. The agency should continue to be open to new approaches and to learning, and not push its own system. Given these developments, the MRA and harmonization can move ahead quickly. Both efforts are important. The MRA can help the harmonization effort by bringing together FDA and the EU, including industry, resulting in confidence building, learning, and longer-term benefits.
I have emphasized the quality systems portion of the MRA, because it is so fundamental for worldwide harmonization and for assurance of device quality. Any new regulatory scheme should be established based on the ISO 9000 series, not on local testing, extensive dossiers, or local requirements that are out of step with international practice.
The second area for action is the need to move toward a universal data set that will satisfy worldwide clinical requirements. Two factors weigh strongly in favor of this goal. In the area of clinical research, most of what is being done in Europe is widely accepted in this country. In fact, European research now makes up the majority of papers presented at many leading medical conferences, and, most importantly, FDA routinely accepts clinical data from European trials in product approval submissions. The other factor is that any company involved today with developing a Class III product tries to create one set of data that can be used universally for all regulatory bodiesthe only way to cost-effectively develop clinical data. However, in doing so, manufacturers often exceed the requirements of any one regulatory authority, and presenting the data differently in numerous submissions is not cost-effective.
We should begin discussions aimed at achieving a harmonized clinical philosophy under which the boundaries of clinical data collection are properly defined and agreed upon, including harmonization of clinical controls. Frankly, this means recognizing, as Europe and various nations have done, that certain datamost importantly, data on cost-effectiveness, relative effectiveness, and medical outcomesshould not be required as part of the product approval process unless explicit claims referring to such are being made. This kind of data is important and has an increasingly appropriate role in healthcare delivery, but not in product approval.
The third area requiring immediate action concerns the recognition of consensus performance standards. These standardsdesigned with the input of industry, government (including FDA), and medical professionalsrepresent state-of-the-art norms for ensuring the safety of medical devices. They are developed at both the international level, by groups such as the International Electrotechnical Commission and the International Organization for Standardization, as well as by groups like the European Committee for Standardization in Europe and AAMI, the American National Standards Institute, and the Underwriters Laboratories in the United States. The standards can be horizontal, applicable to all devices across the board, or vertical, covering only a specific device or type of technology.
Recognition of consensus standards is important because they ensure that products are evaluated according to the best possible criteria. Standards also produce a transparent system, under which manufacturers can know the relevant criteria during the product development process, which increases the efficiency of review. The rapid acceptance of the European regulatory system as an efficient and credible process can be traced in large part to its reliance on consensus standards, together with a procedure for company declarations of conformity.
Domestically, FDA deserves credit for its willingness to move forward, as with the QSR. One of the things to come out of FDA-reform discussions in the last Congress was an agreement by FDA, Congress, and industry that recognition of international standards makes sense and should be a part of any legislative reform. Here, again, FDA deserves credit for acting quickly in this area following passage of the FDA Modernization Act in late 1997. FDA has worked with the National Electrical Manufacturers Association on a pilot program under which FDA accepts certification of compliance with identified consensus standards, such as IEC 601-1 (the safety standard for electrical medical equipment), as part of the 510(k) process. This pilot program has reduced product review times by as much as 50%. Expanding recognition to the fullest extent possible, as FDA is now doing, is critical to moving toward true harmonization.
The fourth area I would like to examine is both an occasion to urge continued progress and a statement of the goal to which I believe we must aspire in our harmonization efforts. The ultimate objective must be a comprehensive MRA covering product approvals for 510(k) devices. The building blocks are already in place, or close to it. They include the acceptance of consensus performance standards, an agreement on quality system regulation, and the accreditation of third partiesincluding some European notified bodiesas part of FDA's pilot project for the performance of product review functions. These three elements would produce a U.S. system for device regulation closely mirroring that of Europe. Both systems could then ensure the highest degree of device safety, while at the same time providing better, more timely access to advanced therapies for the patients who need them.
A series of recent MRA discussions between the EU and FDA have provided opportunities to get this process on the proper footing. I believe these discussions should be aimed at producing an MRA that focuses on the points I have specified: mutual recognition of quality system regulation for all devices, adoption of consensus performance standards, and mutual recognition of approvals by third parties for 510(k) devices.
The final area I want to emphasize is the need for harmonization in Asia. The current situation in Asia is reminiscent of the messy regulatory landscape of Europe in the late 1980s. Each country is developing a unique approach to device regulation, comprising various mixtures of local testing, different data requirements, different products regulated, and, inevitably, too few staff. The result is a fast-growing problem of regulatory overkill, proliferation of divergent requirements, and product-introduction delays. And while there is no convenient organization such as the EC for Asia, HIMA has organized an Asian Harmonization Working Party consisting of regulatory authorities and area managers of U.S. companies. This group should now serve as a forum for discussion of Asian harmonization, including acceptance of a common dossier and ISO 9001 certificates. We can also work on this problem with the assistance of the U.S. government in regional organizations such as Asia Pacific Economic Cooperation (APEC).
The environment is right for efforts between government and industry to produce real progress in these areas. If this comes to pass, both patients and the enterprise of medical research will surely benefit.
Fred S. Halverson is vice president of international regulatory strategy and reimbursement policy at Medtronic Inc. (Minneapolis).