Medical Device Approval in the US and Abroad

FDA regulation and CE Marking represent different approaches to quality control.

By DOROTHY ABEL
 

The views and opinions are those of the author and do not necessarily reflect those of the US FDA, the US Department of Health and Human Services, or the Public Health Service.

Medical device regulation generates quick, but interestingly divergent, criticism. People either feel that regulation is too cumbersome and restricts access to promising technology, or they believe that regulation is too lax and subjects patients to undue risks. Although both criticisms have been applied to FDA device regulation, this system is more often regarded as too restrictive. In contrast, the general opinion of European Union (EU) device regulation is usually considered too lax. This article briefly describes and compares these systems.

INTERPRETATION OF THE LAWS
Both the US and the EU have laws governing medical device regulation, but interpretation and application of these laws differ greatly between the two systems. The Federal Food, Drug, and Cosmetic Act (the Act) and its amendments are the primary laws giving the FDA authority over medical devices. These laws are interpreted in the Federal Register with final regulations codified annually in the Code of Federal Regulations. The FDA also develops guidance to clarify specific requirements of the regulations and is responsible for all aspects of device regulation.

The EU regulates the safety and marketing of medical devices with three Medical Device Directives (MDDs). The primary Directive covers most medical devices; the other two Directives provide specific requirements for im-plantable and in vitro diagnostic devices.

Medical device regulations implement the provisions of the MDDs. Under the provisions, each member country must establish a Competent Authority, a regulatory agency responsible for implementing, monitoring, and enforcing the Directives. Each Competent Authority has the authority to nominate Notified Bodies responsible for verifying that manufacturers conform to the Directives.

CATEGORIZATION OF DEVICES
The FDA and the EU classify devices and impose requirements for devices in each class. The FDA defines classes according to the level of oversight needed to ensure the safety and effectiveness of each type of device. Classification is based on how well the device, its performance, and testing requirements were defined at the time of classification. The level of risk posed by use of the device is also taken into account. Examples of each class are shown in Table 1 in our print version of this article.

All devices are subject to general controls, or baseline requirements of the Act (eg, good manufacturing practices [GMPs], registration and listing regulations, and labeling requirements). However, certain low-risk devices are exempted from compliance with some requirements. Some devices have additional controls, such as special labeling or testing requirements. Finally, other devices must undergo premarket approval (PMA), a more comprehensive clearance process than that required for other devices.

The EU’s MDD classifies devices according to risk level (low, medium, or high), type of body contact (noninvasive, invasive with respect to body orifices, or surgically invasive), duration of body contact (transient, short-term, or long-term), and additional factors such as whether they undergo a chemical change in the body, or supply energy in the form of ionizing radiation. The MDD also assigns classifications for some specific devices, such as those manufactured utilizing animal tissues. See Table 2 in our print version for examples of each class.

BRINGING DEVICES TO MARKET
Devices reach the US market via several routes; the most common routes are the premarket notification approach for class II devices (per section 510[k] of the law) and the PMA process for class III devices. A 510(k) submission includes information demonstrating the new device is as safe and effective as (?substantially equivalent? to) a device that is or was legally marketed in the US, and that does not require PMA. If the information is acceptable, the agency issues a letter stating the device is considered substantially equivalent and may be marketed. The majority of medical devices in the US go through this process.

A PMA application generally contains much more information than a 510(k), usually including clinical data, and must demonstrate the device is reasonably safe and effective. If the FDA receives sufficient data, an approval order is issued and the device may be marketed.

In order for a device to be legally marketed in the EU, the device must have a CE Mark. Before affixing this mark, the manufacturer must certify that the device conforms to the MDD’s essential safety and administrative requirements. For each device class, several conformity assessment procedures may be followed. For class IIa or IIb devices, the manufacturer self-certifies that they have satisfied the requirements of the MDD. However, they must maintain all technical and design files and data, which will then be audited by the Notified Body; the Competent Authority can also request access to the data. For class III devices, the manufacturer must submit a full technical dossier to the Notified Body for review.

CLINICAL DATA REQUIREMENTS
The FDA and EU have different mechanisms to allow for the conduct of clinical studies, but their differences in data requirements are more interesting. The FDA requires an evaluation of safety as well as effectiveness. The MDD focuses on safety plus device performance (the ability of the device to work as described). In addition, if the FDA requires clinical data to support the safety and effectiveness of a device, these data are usually collected under a clinical study (which may or may not be conducted in the US). To conform to the MDD, clinical evidence must be based on a compilation of scientific literature, data from a specifically designed clinical study, or a combination of the two.

SHORTCOMINGS IN BOTH SYSTEMS
Critics of FDA regulation argue that the system is resource-intensive, limits access to technology, and is too prescriptive. Those who criticize the EU approach say that the system is too variable, places too much responsibility on manufacturers, and may allow widespread use of unproven devices.

The shortcomings of each system can also function, in some situations, as advantages. For example, relatively few US citizens were exposed to endovascular graft devices that had problems during clinical evaluation. At the same time, these devices were more widely used in the EU. Although fewer Americans were exposed to a problematic device, if use of these devices had been as restricted in the EU as it was in the US, the technology would be less advanced than it is today. Table 3 in our print version provides an overview of the two systems.

Each system seems to reflect the level of regulation that its audience demands and that is currently plausible. Device regulation in the US has evolved over time. Our system has increased in breadth and depth in response to public and congressional reaction to highly publicized failures. Our relatively risk-averse society expects comparatively strict regulation.

The EU’s effort to standardize device regulation is relatively young. Regulation is difficult under the best of circumstances; given the diversity of cultures, languages, and governments in the EU, their current level of oversight is nothing short of admirable.

To answer the question of which system is best, one must consider whether the device to be marketed is “good” or “bad.” Access to “good” devices is optimized in the EU, whereas the US excels at protection from “bad” devices.

Dorothy B. Abel is a Regulatory Review Scientist at the US FDA Center for Devices and Radiological Health in Rockville, Maryland. Ms. Abel may be reached at (301) 443-8262, ext.165; dba@cdrh.fda.gov.

 

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