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joe et al., regarding medical devices in radiology, please allow me to repost this link, or better yet post the article and emphasize with bold print some interesting parts...

Regulation of Medical Devices in Radiology: Current Standards and Future Opportunities1

John J. Smith, MD, JD
+ Author Affiliations

1From the Department of Radiology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114; Harvard Medical School, Boston; and the Center for Integration of Medicine and Innovative Technology, Boston. Received August 31, 1999; revision requested October 21; revision received November 19; accepted December 17. Supported in part by a grant from the Center for Innovative Minimally Invasive Therapy, a nonprofit consortium consisting of Massachusetts General Hospital, Brigham and Women’s Hospital, Massachusetts Institute of Technology, and Draper Laboratory. Address correspondence to the author (e-mail: [e-mail]).

Abstract

Today’s radiology community depends heavily on cutting-edge diagnostic and therapeutic medical devices to serve patients. These products are regulated by the U.S. Food and Drug Administration (FDA) under a system that grants marketing approval for only those indications for which the safety and effectiveness have been established. Although this complex system is the result of a societal decision to ensure device safety and effectiveness, it has the potential to delay product marketing and impede innovation. Medical device regulation recently has undergone major changes with the enactment of the Food and Drug Administration Modernization Act of 1997 (FDAMA), legislation that is intended to increase system efficiency while retaining the requirement of safety and effectiveness. However, many of the envisioned improvements cannot occur without cooperative interaction between stakeholders in the device development process, including the FDA and the clinical medicine community. The radiology field must continue to build on its strong history of productive dialogue with the FDA to transform the legislative vision of FDAMA into regulatory reality. Such action will ensure timely access to the new device technologies that are necessary for the growth of our specialty and the effective care of our patients.

[INTRODUCTION]
Modern radiology is heavily dependent on the use of state-of-the-art diagnostic and therapeutic devices; thus, timely federal regulatory approval of new devices is crucial to the availability of innovative technology to effectively serve our patients and build our specialty. This regulatory scheme recently experienced major changes with the enactment of the Food and Drug Administration Modernization Act of 1997 (FDAMA) (1). FDAMA, in addition to altering many existing regulatory provisions, has fostered an atmosphere of cooperation and responsiveness on the part of the U.S. Food and Drug Administration (FDA) to address the concerns of clinical medicine and industrial communities. Despite these positive developments, there remain elements of the FDA’s new device evaluation process that pose considerable practical impediments to bringing new technologies to market. It is incumbent on the radiology community to build on its long history of productive interaction with the FDA and use the opportunity for collaboration presented by FDAMA to facilitate positive change in the regulation of the devices that are so important to our patients and the future of our specialty.

HISTORY OF MEDICAL DEVICE REGULATION

Device Regulation before 1976

Comprehensive medical device regulation is a relatively new addition to federal regulations of medical products. Although drugs have been federally regulated since the passage of the 1906 Food and Drugs Act (2), devices were not included in the regulatory framework until the passage of the Food, Drug, and Cosmetic Act of 1938 (FDCA) (3). Even then, the authority to regulate the comparatively simple devices of that time was quite limited—that is, confined to challenging the sale of products believed to be “adulterated” (ie, unsanitary or unsafe) or “misbranded” (ie, bearing false or misleading claims). It is notable that manufacturers were not required to establish the safety and effectiveness of their products prior to marketing them.

Device regulation remained relatively unchanged until the 1960s, when an explosion in technology ushered in a variety of new products, some of which posed substantial potential risks to patients. Facing a possible public health problem and lacking regulatory authority to evaluate medical devices prior to marketing, the FDA crafted a controversial stopgap solution. The FDCA, as modified by the drug amendments of 1962, contained a premarket approval process for new drugs in which a manufacturer was required to establish the safety and effectiveness of a given product before marketing it (4). Building on this drug-based regulatory authority, the FDA classified as drugs a number of products that were arguably devices and applied the premarket approval requirements. This policy was frequently upheld by the courts (5,6). However, it was difficult to apply on a large scale, and an active search for a more structured approach was begun.

Congress acted to regulate medical devices that emitted radiation by passing the Radiation Control for Health and Safety Act of 1968, which was designed to protect the public from excessive radiation exposure (7). This legislation, which applied to any radiation-producing product, including consumer items and industrial tools, gave the FDA the power to develop and enforce performance standards for diagnostic x-ray equipment, medical lasers, and ultrasonographic (US) therapy equipment.

The need for more comprehensive medical device regulation led to the formation of the Cooper Committee, a federal committee charged with exploring possible regulatory solutions (8). In its 1970 report, this committee observed the wide range of risks and complexities of medical devices and concluded that these products should not be regulated with a single approach, as was done with drugs. The report recommended a new tiered regulatory system, in which devices that posed a higher perceived risk to patients would be subject to more demanding requirements than those that posed a lower level of risk.

Medical Device Amendments of 1976

The Medical Device Amendments of 1976 (MDA) were intended to ensure that devices are safe and effective for the indication(s) for which they are legally marketed (9). The MDA, following the Cooper Committee’s recommendations, mandated a risk-based three-tiered system for device regulation that is still in use today. Under this legislation, all medical devices legally marketed prior to the implementation of the MDA on May 28, 1976, are placed into one of three classes with the assistance of expert advisory committees.

Class I devices are those that are not purported or represented to be for a use that is of substantial importance in preventing impairment of human health and that do not present a potentially unreasonable risk of patient injury. Devices in this category are not individually regulated, but they are subject to “general controls”—that is, regulations designed to ensure the safe manufacturing and correct labeling of all medical devices. As such, general controls apply also to class II and class III devices. Examples of class I products are lead gonadal shields and x-ray grids.

Class II devices present a greater risk of harm than do class I devices and may be subject to additional regulation in the form of “special controls,” which are applied to specific device types. As with class I products, there is no individual regulation of these devices. Examples of class II devices include higher technology products that do not by themselves maintain life, such as diagnostic angiographic catheters and many diagnostic devices, including computed tomography (CT), magnetic resonance (MR), and US imaging units.

Class III products include high-risk devices that are “represented to be for use in supporting or sustaining human life or for a use which is of substantial importance in preventing impairment of human health,” or that “presents a potential unreasonable risk of illness or injury” (9). All products in this class are individually regulated and subject to a premarket approval process in which the manufacturer is required to establish the safety and effectiveness of the device before marketing it. Devices in this category include vascular stents and detachable endovascular coils.

The MDA further divides devices into those that were legally marketed before implementation of the legislation on May 28, 1976—pre-1976 devices—and those that were marketed after that date—post-1976 devices. Pre-1976 devices can continue to be legally marketed without additional approval from the FDA, although class III products are subject to future FDA demands for safety and effectiveness data.

New post-1976 devices are evaluated before being marketed under the MDA premarket notification requirement, which is commonly known by its FDCA section number, 510(k). Section 510(k), as originally enacted, required manufacturers to notify the FDA of their intention to market essentially any new product. If the FDA determined that the new device was “substantially equivalent” to a pre-1976 product, the product was placed in the class of its “predicate” product, which is a term used by the agency to denote a legally marketed existing product to which a new device may be substantially equivalent. Citations in the peer-reviewed literature and the expert opinion of physicians played an important role in the determination of substantial equivalence. With substantial equivalency established, the new device could then be marketed immediately, under the existing regulations imposed on the predicate product. New products introduced after 1976 that lacked predicates were automatically placed in the class III category and subject to a premarket approval process that generally required clinical trials.

Section 510(k) did not include a definition of “substantial equivalence,” so the FDA was left to define the term. Most commentators agree that the FDA focused on the comparability in operation and clinical use between the two devices when determining substantial equivalence (10). The agency usually did not require clinical trials to establish comparability and declare a product substantially equivalent. The agency further broadened section 510(k) by introducing “piggybacking”—that is, allowing post-1976 devices that were judged to be substantially equivalent to pre-1976 products to serve as predicate devices (10). This policy effectively permitted evolutionary change in predicate devices without subjecting incrementally changed products to the more demanding premarket approval process.

Helical CT is an example of device evolution that was permitted under the FDA definition of substantially equivalent (11). Developed in the late 1960s and legally marketed prior to 1976, conventional CT scanners were considered to be pre-1976 products and placed in the class II category. Helical scanning represented a significant change in the method by which images were obtained, although the overall operation and use of the technology were very similar to those of the existing products. The FDA focused on these similarities to determine that the safety and effectiveness of helical CT paralleled those of conventional CT. After evaluating laboratory and clinical data, the FDA determined that helical CT was substantially equivalent to existing CT technology and permitted the marketing of the helical device as a class II product.

Device Regulation between 1976 and 1997

The MDA represented a major expansion in the regulation of medical devices and imposed a considerable new administrative burden on the FDA. Although many of the regulatory mechanisms in the MDA were patterned after established drug regulatory tools, their application to devices raised new issues. For example, the premarket approval process developed for drugs was not directly transferable to devices. Adding to the problem was the challenge of developing a comprehensive device regulatory process where a relatively limited program had been in place—an exercise that strained agency resources. During the next 2 decades, the FDA and Congress continued to face challenges in fully implementing the vision of the MDA.

Congress revisited medical device regulation in 1990 with the Safe Medical Devices Act of 1990 (12). This legislation was intended primarily to strengthen the FDA’s authority to monitor marketed products (11,13). The act also required the FDA to affirm a device’s substantial equivalence before marketing and recognized the agency’s authority to request clinical data to establish substantial equivalence for devices that differed in technology or design from the claimed predicate product. Two years later, Congress enacted the Medical Device Amendments of 1992 (14). This legislation was designed to clarify the Safe Medical Devices Act of 1990 and largely technical in nature; the regulatory framework of the initial legislation was essentially unaltered (15).

Before the early to middle 1990s, the device regulatory system established by the MDA, as amended in 1990 and 1992, functioned differently from the rigid single-path regulatory framework in place for new drugs (10). This was not surprising for the lower risk class I and II products, which were generally approved with 510(k) applications and not subject to premarket approval system regulations. However, even the relatively high-risk class III products usually were not subject to the same rigorous scrutiny applied to drugs, which ordinarily involved three discrete phases of clinical testing to establish safety and effectiveness. In addition, device trials infrequently featured the double-blind placebo-controlled study design that was generally acknowledged to constitute the “gold standard” for new drug clinical testing.

FDA evaluation of devices became a national issue in the early 1990s, however, when safety concerns regarding silicone breast implants received widespread publicity. These pre-1976 devices and their substantially equivalent post-1976 “cousins” were legally marketed under the pre-1976 class III provisions and had not been formally evaluated for safety and effectiveness. Fueled by considerable media attention, the controversy quickly spread from a focus on implants to an investigation of the entire device regulatory system—in particular, the science underlying the evaluation of safety and effectiveness.

The FDA responded to the controversy by organizing the Committee for Clinical Review to study device evaluation; this group consisted almost exclusively of FDA employees responsible for drug evaluation (16). In its final report, the “Temple committee,” as it became known, concluded that the fundamental principles underlying the evaluation of any therapeutic intervention, whether drug or device, should be the same. Furthermore, the committee did not recognize any distinction between studies designed to demonstrate substantial equivalence under section 510(k) and those intended to show safety and effectiveness in the premarket approval process. These findings combined had the potential to alter the FDA’s basic approach to medical device evaluation and substantially increase the regulatory burden of 510(k) requirements for substantial equivalence, which were traditionally less demanding than the premarket approval applications. Then FDA Commissioner David Kessler, MD, endorsed the report and promised to ensure the implementation of its recommendations (10).

In the aftermath of the silicone implant controversy and the Temple report, the FDA began to introduce changes that some commentators contend blurred the distinction between evaluation of new devices and evaluation of new drugs (10). Regardless of the underlying philosophy, there was no doubt that FDA scrutiny of devices had increased and with it, the amount of data and time required to bring new products to market. Delays in securing marketing approval resulted in substantial criticism from physicians, the medical device industry, and Congress (15,17). The 1994 Congressional elections, which established Republican majorities in both the Senate and the House of Representatives, set the stage for action directed at repairing what some contended had become an unnecessarily burdensome device regulatory system. The FDA responded to this pressure by instituting a “reengineering” effort, under which various initiatives were undertaken to improve regulatory efficiency. However, this program did not fully satisfy FDA critics, who continued to push for new legislation.

Food and Drug Administration Modernization Act of 1997

Efforts to reform the device regulatory system culminated in FDAMA, which was signed into law on November 21, 1997 (1). This legislation does not alter the statutory requirement that devices be safe and effective for their approved indications. Rather, its goal is to improve regulatory efficiency by building on administrative reforms already underway at the FDA and ensuring greater agency accountability through a plan for compliance (18,19). As part of this process, the aim of FDAMA is to increase cooperation and communication between the FDA and those affected by the regulatory system, such as physicians and the industrial community. Specific FDAMA provisions address a number of issues, such as focusing FDA resources on high-risk devices, improving the efficiency of device evaluation, speeding up the introduction of important new technologies, and addressing the off-label use—that is, use for indications other than those on the FDA-approved labeling or package insert—of approved devices.

Focusing on high-risk devices.

—Under FDAMA, the FDA focuses its resources on high-risk devices through various provisions. Section 206 exempts the majority of class I and many class II products from premarket FDA notification under section 510(k) and reserves the process for higher risk products. Under section 210, parties outside of the FDA may be accredited to review class I and lower risk class II device premarket notification applications, so that the FDA is able to concentrate on higher risk class II and high-risk class III products. Sections 207 and 416 contain provisions to reclassify devices, in particular, genuinely new products (with no predicate devices) that are automatically considered as class III devices. Although it remains to be seen how the latter provisions will be applied, they presumably will be used to expeditiously move lower risk products from class III designation, which requires so much agency attention.
Improving the efficiency of device evaluation.

—A variety of FDAMA provisions function to improve the overall efficiency of the device evaluation process. Section 205 requires the FDA to consider the “least burdensome” means of evaluating effectiveness that would have a reasonable likelihood of resulting in approval for both 510(k) and premarket approval applications. Section 201 allows the FDA to use data from previous clinical trials to support the applications of subsequent devices under certain circumstances. For those devices that necessitate clinical trials, section 217 specifically states that “reasonable assurance of effectiveness” may be demonstrated by the results of only one well-controlled clinical investigation, where appropriate (1). Section 404 mandates that to address significant scientific controversies that develop between the FDA and those it regulates, the agency is required to establish a dispute resolution process. Finally, section 204 explicitly incorporates standards into the evaluation process; this provision allows the FDA to recognize consensus standards and use them in product reviews.

Several provisions of FDAMA focus on specific types of applications. For example, section 209 establishes a 90-day time frame during which the agency must make an initial classification decision on 510(k) submissions for devices that have not been previously classified. This provision is clearly directed at the substantial delays in processing 510(k) applications that arose in the middle 1990s.

The concept of a binding meeting was introduced for products that are subject to premarket FDA approval and certain other products. Section 201 allows a sponsor of a class III, or implantable device, to request an “agreement” meeting, during which the FDA and the sponsor agree to a binding investigational plan. Unilateral FDA action to change the agreement is allowed only when a substantial scientific issue that is essential to determining the given product’s safety and effectiveness subsequently develops. A binding meeting to agree on the type of evidence needed to support premarket approval of a device, known as a “determination” meeting, is provided for in section 205. Like section 201, the results of this meeting commit the FDA to a course of action, in the absence of a subsequent determination that the agreement is contrary to public health.

Section 205 authorizes the FDA to use postmarket controls in evaluating either a 510(k) or premarket approval application. This provision presumably allows the agency to expedite marketing approval by requiring some type of postmarket evaluation process.
Expedited introduction of important new technologies.

—Section 202 provides for a priority review of certain devices. These include devices (a) that represent breakthrough technologies, (b) for which no approved alternatives exist, (c) that offer substantial advantages over approved therapies, and/or (d) for which availability is in the best interest of patients. In addition, section 402 allows expanded patient access to investigational therapies and diagnostic techniques under specified conditions.

Off-label use of medical devices.

—The FDCA regulates the marketing of medical devices but not their use by licensed physicians. Devices and other medical products are commonly used for indications other than those contained in their FDA-approved labeling or package insert, a practice known as off-label use. An example is deploying a stent that is approved for use in the iliac arteries in the iliac veins. For years, the FDA has acknowledged the right of health care providers to engage in such use under the “practice of medicine doctrine”; however, the concept was never formalized in the statute or implementing regulations (20–23).
Section 214 of FDAMA explicitly acknowledges the practice of medicine doctrine in the context of medical devices. It prohibits the FDA from interfering with the authority of a health care practitioner to prescribe or administer any legally marketed device for any condition or disease within a legitimate practitioner-patient relationship. This provision appears to codify the long-standing FDA deference to off-label use; this is supported by an explicit disclaimer stating that the section does nothing to limit existing FDA regulatory authority.

Section 401 addresses the problematic issue of manufacturer distribution of information with off-label use; such distribution was substantially limited by the FDA prior to FDAMA (24,25). The new provision allows such distribution, but only when a manufacturer agrees to submit a supplemental application for that off-label use or the FDA explicitly waives the requirement. Although the FDA’s regulations to implement these provisions were the subject of an initially successful legal challenge, a subsequent appellate decision reversed the Federal district court and apparently upheld the legality of the provisions (26).

CURRENT MEDICAL DEVICE REGULATION SYSTEM

Regulatory Treatment of New Devices

The decades-long process of establishing a comprehensive device regulatory system that began with the MDA has culminated in a complex system designed to ensure that medical devices are safe and effective for their FDA-approved indication(s). It is a system that focuses on the marketing of products, not on their ultimate use by health care professionals. To understand the operation and inherent problems of this system, it is useful to trace how a new medical device secures FDA marketing approval for a specific clinical application.

Premarket notification–exempt class I and class II devices may be legally marketed without first informing the FDA. These products must be in compliance with general controls, which are a collection of agency regulations that are applicable to all medical devices and designed to ensure that products are safely manufactured and correctly labeled (27). General controls include prohibitions against misbranding and adulteration, as well as requirements for reporting and record keeping. Manufacturers must register with the FDA, comply with labeling requirements, and design and produce devices by using “good manufacturing practices”—that is, requirements designed to maintain quality in the manufacturing process. Class II products may be subject to additional regulation in the form of special controls. Marketing of a gonadal shield, an exempt class I product, illustrates the operation of this system for all premarket notification–exempt class I and class II devices. A registered device manufacturer seeking to market this product needs only to manufacturer and label the shield in accordance with applicable general controls before distributing it. Sales may then commence without formal notification to the FDA.

Nonexempt class I and class II, class III, and all genuinely new products are subject to the premarket notification provisions of section 510(k). Manufacturers of these products must submit applications describing the indication(s) and use(s) of the device, as well as data to support a claim of substantial equivalence to a predicate device. These data generally do not involve clinical trials, but such trials may be required. Should the FDA determine that the new device is substantially equivalent, it is classed with its predicate and becomes subject to identical regulatory requirements. This is relatively straightforward when the predicate device is in class I or class II, because these products are not individually regulated and a manufacturer needs only to comply with the existing regulations that are applicable to the product. For example, the manufacturer of a new CT scanner typically has to submit engineering specifications on the performance and safety of the unit as part of a 510(k) application to support the contention that the new device is substantially equivalent to previous CT scanners. Once this equivalence has been established, the new unit may be marketed and is subject to existing regulations applicable to CT scanners.

Products with a class III designation are more complicated. If the predicate is a pre-1976 product for which the FDA has not requested premarket approval data, the substantially equivalent new device may be legally marketed until the agency requests such data and either the manufacturer fails to provide it or the supplied data do not demonstrate reasonable safety and effectiveness. Should the predicate have been subject to the premarket approval process, the manufacturer of the new product must generally submit data supporting its safety and effectiveness, because data from previous premarket approval submissions are considered proprietary.

New medical devices without a predicate are automatically placed in the class III category. It is possible to reclassify such a product by means of petition by either the manufacturer or the FDA on its own initiative, providing that there are data indicating that regulation of the device as a class I or II product would be sufficient to reasonably ensure safety and effectiveness. An example of a reclassified product is the standard MR imaging unit, a post-1976 device that was originally designated a class III product and marketed by using the premarket approval process. The modality was subsequently down classified to class II after the results of several years of studies demonstrated that it did not pose a substantial risk to patients (10). In the absence of such data or when a device meets the FDCA definition of a class III product (ie, “represented to be for use in supporting or sustaining human life or for a use which is of substantial importance in preventing impairment of human health” or that “presents a potential unreasonable risk of illness or injury” [9]), it remains in class III and is subject to the premarket approval process.

Premarket approval of post-1976 class III devices necessitates demonstration of reasonable safety and effectiveness before marketing. A similar standard applies to pre-1976 class III products for which the FDA has requested data; however, these products generally may be marketed while data are being gathered. Establishing a device’s safety and effectiveness often necessitates human clinical data, the type of which is determined on a device-specific basis. These requirements may be satisfied by using a single study, where appropriate. An experimental design is conceived by the device’s sponsor, usually in consultation with expert physicians and scientists, and approved by the FDA and the individual investigational review boards at the participating institutions. The device is distributed to the clinical centers that are conducting the trial(s) under an investigational device exemption, which allows interstate distribution of the device exclusively for use in the trial. The resultant data are then analyzed by the FDA to determine whether safety and effectiveness have been established.

The overall time frame for determination of substantial equivalence under section 510(k) or marketing approval under the premarket approval process is variable and heavily dependent on the product at issue. In most situations, and particularly those involving clinical data, the FDA encourages early sponsor contact with the agency to ensure that the data collected meet statutory requirements. In general, 510(k) applications for which no clinical data are required receive relatively rapid FDA determinations, whereas 510(k) or premarket approval applications that necessitate clinical data take substantially longer. As of the fiscal year 1999, the average FDA review time for 510(k) applications was 74 days, with a comparable figure for premarket approval applications, 12 months (28). It is notable that these times do not include the sponsor time spent gathering data, preparing the application, and addressing FDA requests for additional data.

Data collection requirements may not end with marketing approval for high-risk class II and class III products, because section 522 of FDAMA allows the FDA to require postmarket surveillance. The agency has recognized the need to collect such data when there are important unanswered questions and a postmarket approach is practical (29). Such approaches may include detailed review of complaint history and scientific literature, nonclinical testing, follow-up of a defined patient sample, use of existing secondary data sets, use of registries, and/or even follow-up clinical trials. The requirements for and type of postmarket surveillance are device-specific and determined at the time of marketing approval.

Importance of FDA Marketing Approval

FDA approval of a new medical device allows a manufacturer to commercially distribute and market a product for the application(s) included on the approved labeling or package insert. However, the practical implications of FDA approval for a given application reach beyond the obvious benefits.

Since 1986, the Health Care Financing Administration (HCFA), the federal agency that oversees the Medicare program, has maintained a general policy that reimbursement for procedures and services that involve the use of medical devices will be provided only if the device is FDA approved for the indication in question (30). This policy, which reflects a statutory prohibition against paying for experimental therapies, has been followed by many other third-party payers. Over the years, this general prohibition has been gradually relaxed. Initially, an FDA-HCFA agreement allowed for reimbursement of devices that are undergoing clinical testing under certain limited circumstances (31). In 2000, President Clinton directed HCFA to provide reimbursement for “routine” medical care associated with clinical trials, although coverage for the experimental devices themselves is subject to the existing FDA-HCFA agreement (32). Still, in practical terms, off-label and experimental use of medical devices creates considerable reimbursement questions for providers and institutions.

FDA marketing approval has been used by plaintiff attorneys as a de facto medical standard of care. Specifically, it has been maintained that the use of a medical device for an indication that lacks FDA approval is experimental. Although this contention ignores the traditional legal distinction between the medical standard of care established by physicians and an FDA regulatory decision based on statutory criteria, it has appeared in a number of lawsuits (33–37). The result has been heightened awareness by physicians, administrators, and risk managers of the potential legal pitfalls of off-label use. There have been anecdotal reports of such use being restricted or prohibited by hospital lawyers or risk managers (JJ Smith, MD, JD, ME Jensen, MD, JE Dion, MD, unpublished data, 1996). Although the effects of potential legal liability linked to off-label use are difficult to quantify, there is little doubt that they have limited off-label use of medical devices.

DISCUSSION

Inherent Problems Facing the Device Regulatory System

FDA regulation of medical devices is a complex indication-specific approval system designed to ensure the safety and effectiveness of products for their marketed indication(s). Although this system reflects a societal decision to ensure the safety and therapeutic benefit of medical products, it also creates an environment with the potential to stifle technical innovation. Potential obstacles to such innovation include the indication-specific nature of marketing approval, the considerable latitude given the FDA in evaluating new products, and the treatment of genuinely new medical devices.
Indication-specific device approval is an inherent component of any regulatory system designed to ensure therapeutic effectiveness. However, providing data, particularly clinical information, to support marketing approval for a clinical indication is time-consuming and costly. Furthermore, the practice of medical doctrine allows physicians to routinely use devices off label. The result is an environment in which manufacturers may lack the incentive to secure FDA approval for additional clinical indications beyond the single indication necessary to gain market access.

Further complicating this environment is the complex, somewhat restrictive FDA policy governing manufacturer dissemination of information on off-label use. To avoid potential regulatory violations, most companies have elected a cautious approach. Distribution of materials, usually journal articles, on off-label use typically occurs only when such information is explicitly requested by a health care provider. Even then, the provided literature generally includes an explicit disclaimer that the use described is not FDA approved and that the company does not support or recommend such use. Industries are very reluctant to provide additional information or product support for off-label use, particularly from their sales force, owing to fear of being seen as a promoter of the nonapproved use.

Given that manufacturers are often in the best position to inform practitioners of the various uses of their products and that the current regulatory climate substantially limits the dissemination of information for nonapproved indications, state-of-the-art therapies based on off-label use of existing products may be slow to diffuse into widespread clinical practice. In addition, the lack of FDA approval for a specific clinical application may complicate efforts to obtain third-party reimbursement or raise risk management questions that may lead to limited off-label use.

The FDCA is vague in its requirements for new device approval: It states only that there must be “reasonable assurance” of safety and effectiveness. The day-to-day definition of this standard is determined by the FDA; this is a prudent decision in an environment where continuing scientific advancement can rapidly change the methods by which devices are evaluated. However, medical devices are in many ways different from other products that are evaluated by the FDA. Most devices undergo constant evolution and have relatively short product life spans, and the engineering problems encountered during clinical use generally are sequentially addressed and resolved. In many instances, these devices are medical tools with clinical results that are heavily dependent on the skill of the physicians using them. In comparison, drugs go largely unchanged throughout much longer product life spans, and their therapeutic effects typically are less dependent on the physicians prescribing them.

Given the differences between drugs and devices, a uniform approach to device evaluation based on the FDA’s experience with nondevice products is likely to result in inappropriate clinical trial designs with the potential to slow or defeat marketing approval applications. For example, the double-blind placebo-controlled study that serves as the reference standard for drug evaluation is difficult or impossible to duplicate with devices, with which a procedure is generally necessary to use the product and the treating physician almost certainly knows whether the therapeutic intervention is being applied. In a similar respect, end points of medical device clinical trials to evaluate effectiveness must be adjusted to allow for operator experience and skill.

Treatment of genuinely new medical devices without predicates is problematic with the current regulatory system. These products are automatically considered to be class III devices, which technically must have premarket approval before they can be legally marketed. Down classification provisions do exist under FDAMA, but it remains to be seen how aggressively they will be applied in practice. For products that legitimately belong in other classes, there is the potential for considerable delay of their clinical application while data to support their reclassification are being gathered and administrative consideration is being given to the down classification process.

New devices that legitimately belong in class III, which are subject to the premarket approval process, also face potential considerable delays in clinical use for the reasons previously described. In either case, the clinical application of important new technology may be delayed. The elaborate process by which genuinely new products are evaluated by itself may discourage the development of truly innovative products, particularly that by smaller firms with limited resources, because the industrial community balances what is technically possible with what is more likely to gain timely marketing approval.

A Framework for Solutions to Regulatory Problems

The current regulation of medical devices reflects a societal decision to ensure the safety and effectiveness of medical products for their marketed indication(s), a principle that is very unlikely to be altered. Like any regulatory system, the current medical device regulation system has the potential to negatively affect the market it controls. However, FDAMA, with specific provisions and the general climate of cooperation and communication that it engenders, presents an opportunity for radiologists and the organized radiology community to continue their strong working relationship with the FDA to maximize the efficiency of the existing regulatory framework. In particular, the long-standing productive cooperation between the FDA and organizations such as the American College of Radiology, the Radiological Society of North America, and the Society for Cardiovascular and Interventional Radiology may serve as a foundation for affecting positive change through FDAMA.

The current indication-specific approval process can be improved to expedite the approval of important, state-of-the-art products as well as to minimize agency resources directed at evaluating relatively less important, lower risk products. The FDA has already acted to down classify a number of devices from class III to class II and thus lessen the regulatory burden on these devices (38). The radiology community must support these efforts and could take the initiative in suggesting additional specific products to be down classified. In addition, the support of our community in FDA efforts to establish outside review of 510(k) applications can contribute to the success of this program by helping to free FDA resources so that it can concentrate on high-risk products.

The availability of state-of-the-art technologies may be further enhanced by the aggressive use of FDAMA provisions to expedite the introduction of important new technologies. It is important that radiologists function as advocates for their patients when they believe that a new product represents a genuine breakthrough or when no viable alternative is available. Without such aggressive participation, the effect of these provisions is likely to be considerably lessened.

FDAMA, in conjunction with recent litigation, has created an opportunity for practical regulation of manufacturer distribution of information on off-label use. Such a solution carries with it the promise of moving state-of-the-art off-label uses into mainstream radiology practice more quickly. The radiology specialty societies, in conjunction with the industrial community and the FDA, can play an important part in successfully implementing the regulation of information on off-label use.

FDAMA directs the FDA to consider the least burdensome method of approving a new device, language that reflects the legislation’s overall goal of improving regulatory efficiency. The radiology community can play a major role in defining this largely undefined term by incorporating FDAMA’s mandate to recognize consensus standards. If properly defined and applied, the concept of least burdensome, with integrated device evaluation consensus standards, can speed up the introduction of new medical devices by describing how specific devices are to be evaluated. This ensures the appropriateness of the science applied to product evaluation while increasing the predictability of the process.

Finally, FDAMA down classification provisions may substantially address the problem of genuinely new devices without predicate products. Members of the radiology community can play a key role in assisting the FDA as the agency implements this concept, both with an overall framework and in the evaluation of specific products. In addition, because the least burdensome requirement is applicable to either 510(k) or premarket approval applications, it may be used in conjunction with the down classification provision to develop a comprehensive approach to the problem of genuinely new devices.

CONCLUSION

Modern medical device regulation under the FDCA is a complex endeavor with an inherent risk of impeding the development of new technology. FDAMA was enacted to combat this risk and establish mechanisms by which the overall regulatory goals of safety and effectiveness are maintained while the process itself is made more efficient. The legislation has also fostered an attitude of cooperation and communication between the FDA and the stakeholders in the device development process. However, the regulatory tools established by FDAMA cannot function by themselves or even with the enthusiastic support of the FDA: They are dependent on radiologists and the radiology community working with the agency to make a more efficient and workable regulatory system a reality.


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