FDA and EU Overview

EU and FDA Approval Process of Medical Devices

Both the European Union (EU) and United States call for thorough manufacturing and regulatory practices to establish surveillance systems and other measures to ensure the quality and safety of medical devices. (A medical device is defined as any instrument, apparatus, appliance, software, material or other article, whether used alone or in combination…for the purpose of diagnosis, prevention, monitoring, treatment or alleviation of disease.) Each regulatory body works to improve patient access to innovative medical care and while there are no appreciable differences in safety records between the two, there is a significant difference in time to bring the device to market. As a result, reports suggest that European patients have access to many medical devices earlier than American patients.

The process for which medical devices receive regulatory approval in both Europe and the U.S. is complex. Medical devices need a scientific review to ensure the device’s quality, performance and safety and must also present wide-ranging data to secure a 501(k) clearance in the U.S. and a CE markA European standard for medical devices; a CE Mark indicates that a device meets the requirements of the Medical Device Directive, including consumer safety health or environmental requirements and appropriate quality system standards. The letters “CE” are the abbreviation of French phrase “Conformité Européene” which literally means “European Conformity”. certification in Europe. Also important to note is that while the FDA and EU regulate medical devices and drugs, neither body regulates the practice of medicine.

FDA Approval Typically Lags EU Approval by More Than 2 Years

There are differences between the approach taken to reviewing and approving new medical devices in Europe and the U.S. The centralized approach to medical device approvals taken by the FDA is fundamentally different than the decentralized model the European Commission (EC) has implemented with a significant impact on the approval process, requirements and timing. As a consequence of differences in approach, many observers have pointed to the outcome that new medical devices, and in particular the most novel devices, such as those approved under the Pre Marketing Approval (PMA) process in the U.S., are almost always approved in Europe well before the U.S.

These device approval delays are often avoided in the decentralized model to the benefit of patients and health care workers. As noted by Eucomed Chief Executive John Wilkinson, the system of certification in the EU has given patients and consumers in Europe the fastest access to the most innovative devices with the highest quality and safety standards in the world.

A study conducted by Dr. Josh Makower, one of America’s leading medical technology entrepreneurs and consulting associate professor at Stanford’s Biodesign Innovation program, demonstrated that the FDA delays approval by two years, on average, for low-to-medium-risk medical devices, compared with Europe; approval of high-risk devices in the U.S. took 3 ½ years longer than in Europe.

EU Approval Process Does Not Sacrifice Safety

However, despite the swiftness of the privatized European device approval process, there have been no sacrifices in patient safety according to a recent report. The study, “EU Medical Device Approval Safety Assessment,” conducted by the Boston Consulting Group, matched four years of medical device recall data for the United Kingdom, Germany, Switzerland, and Ireland and compared it with similar U.S. data. The report’s authors conclude that there is no material difference between the regulatory regimes in the U.S. and Europe, from a safety perspective.

The results suggest that, in terms of recall rates, earlier approvals by the EU have not compromised patient safety. In fact, given that the EU likely approves more devices than the U.S., the European recall rate may actually be slightly lower than the U.S. rate.

FDA Process

In the U.S., the evaluation and approval of medical devices is the responsibility of the Food and Drug Administration (FDA) through its Center for Devices and Radiological Health (CDRH), which has a Division of Cardiovascular Devices. As in Europe, devices are categorized by risk into three classes, and higher levels of evidence including clinical evidence are required for approval of devices in Class III. Class III products (e.g., deep-brain stimulators and implantable cardioverter–defibrillators) require clinical studies evaluating the safety and effectiveness of the device, called a Premarket Approval (PMA) application. The FDA in 2010 granted 19 premarket approvals — the type of clearance required for the most highly regulated devices — down from 48 in 2000.

Class III devices that arise from changes to previously PMA-approved devices may not need additional clinical studies. In addition, some older class III devices for which the FDA has not specifically called for PMAs can receive clearance through the 510(k) pathway. The average time to win an approval through the less stringent 510(k) pathway, which is used for most devices, rose to 116 days in fiscal year 2008 from 97 days in fiscal year 2002. Devices that treat rare disorders (fewer than 4000 patients annually) may receive a Humanitarian Device Exemption and be approved on the basis of “probable” benefits, a more flexible standard that recognizes the difficulty of studying patient populations with small numbers and limited treatment options.

Since the FDA requires adequate preclinical safety data before the initiation of human trials, there may be a lag of several years after the introduction of some devices for clinical use within Europe before they are used in patients in the U.S.

EU Process

The current EU system is governed by three European Commission (EC) directives: the Medical Device Directive, the In-Vitro Diagnostic Directive, and the Active Implantable Medical Device Directive. Guidelines for approval are laid out in these EC directives, but the actual approval systems are coordinated at the country level. Each country’s Competent Authority (CAs) certifies “Notified Bodies,” standards organizations that are authorized to approve a variety of goods for the EU market and grant a CE mark certification. Among the current Notified Bodies, there are 70 separate entities across 27 countries with the authorization to approve medical devices for the EU market. A manufacturer seeking to market a new medical device in the EU must select one of these Notified Bodies to certify the new device applications with the CE mark. Based upon the device classification the NB will request certain materials (e.g. a literature review or clinical data) and perform manufacturing quality assessments on the manufacturing process. Upon satisfactory review and approval, a CE mark is awarded, enabling access to the entire EU market.

Any manufacturer wishing to obtain approval to market a new device in a medium- or high-risk group (classes IIa, IIb, III) must undergo a ‘conformity assessment procedure’ involving one or more Notified Bodies. The manufacturer must demonstrate safety and conformity with the legal requirements contained in the first annexes of the three directives.

Key Differences Among the Regulatory Agencies

A significant difference between the two bodies is the EU regulator approves a medical device based primarily on safety, not clinical efficacy. The view in Europe is that the regulator should not be determining clinical efficacy, which is seen to be in the hands of the doctor. Also, while a central governmental agency, the FDA, holds regulatory oversight in America, European approvals are handled by third parties (Notified Bodies).

Another notable difference is patient access to high-risk medical devices. For devices supported by favorable clinical data, EU patients will have enjoyed these options before similar patients in the U.S. For example, two devices for transcatheter aortic-valve implantation (TAVI) have had CE marks since 2007. Later, in a study involving patients with inoperable severe aortic stenosis, TAVI was shown to reduce mortality in absolute terms by 20 percentage points at one year, as compared with standard therapy, with a favorable effect on quality of life. On the basis of these data, the FDA approved one TAVI model in late 2011. In the U.S., truly new but high-risk devices may be available at an early stage only through a humanitarian exception or as part of a clinical trial.

Patients in countries recognizing EU standards will ultimately have access to new, complex technologies earlier than patients in the United States (in some cases, several years earlier; as estimates vary among reports). This fact is paramount for patients with “no-option” CAD (coronary artery disease).

Further Reading on EU/FDA Comparison

The following articles provide more information on the EU/FDA comparison.

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