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7 Conclusions and Recommendations A s noted in Chapter 1, the committee was charged by the Food and Drug Administration (FDA) to review the 510(k) clearance process and answer two principal questions: Does the current 510(k) clear- ance process optimally protect patients and promote innovation in support of public health? If not, what legislative, regulatory, or administrative changes are recommended to achieve the goals of the 510(k) clearance pro- cess optimally? To address its charge, the committee took a multipronged approach in its evaluation of the 510(k) clearance process, as summarized in Chapters 2–6. Aspects of the 510(k) process and other relevant factors that were evaluated include the following: • he legislative history of the 510(k) process. T • he 510(k) regulatory framework that resulted from legislation. T • ow the 510(k) process fits into the larger medical-device regula- H tory framework. (The 510(k) clearance process is an integrated component of the larger medical-device regulatory framework. The committee elected to evaluate the 510(k) program in the context of this larger framework.) • ow the 510(k) process is currently implemented by the FDA. H • vailable postmarket information on the safety and effectiveness of A 510(k)-cleared devices. • ther factors that affect medical-device regulation (for example, the O process of innovation and the medical-device ecosystem in the United States and in other jurisdictions). 189
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190 MEDICAL DEVICES AND THE PUBLIC’S HEALTH The body of evidence gathered from the committee’s evaluations influ- enced its deliberations. The conclusions and recommendations presented in this chapter are the results of the committee’s deliberations. PROTECTING THE PUBLIC’S HEALTH BY ENSURING THE SAFETY AND EFFECTIVENESS OF MEDICAL DEVICES To assess whether the 510(k) clearance process is protecting the public’s health by providing reasonable assurance that marketed Class II medical de- vices are safe and effective, the committee explored two avenues. The com- mittee studied 510(k)-related legislation to determine whether the statute governing the 510(k) program provides for the FDA’s goals for this program (described below). The committee also evaluated available information on the safety and effectiveness of marketed medical devices. The Regulatory Framework of the 510(k) Program As outlined in Chapters 2 and 4, the committee found a substantial disconnect among the committee’s statement of task, the Center for Devices and Radiological Health (CDRH) statement of the goals of the 510(k) clear- ance process, and the FDA’s statute governing the 510(k) clearance process. The committee’s statement of task reads: The current 510(k) process reflects the statutory framework and the U.S. Food and Drug Administration’s (FDA) implementation of the framework; it is intended to meet two important goals: 1) make available to consum- ers devices that are safe and effective, and 2) promote innovation in the medical device industry. Similar language describing the goals of the 510(k) process are included in the CDRH Preliminary Internal Evaluations, Volume 1—510(k) Work- ing Group Preliminary Report and Recommendations (FDA, 2010a, 128), which states that the aim of the 510(k) program is two-fold: (1) to assure, through a quality review process, that marketed devices, subject to general and applicable special controls, provide a reasonable assurance of safety and effectiveness; and (2) to foster innovation. However laudable those goals may be, they are not the purposes that Congress embedded in the 510(k) program (Findings 2-2 and 2-5). In practice, the assessment of substantial equivalence generally does not require evidence of safety or effectiveness of a device. Unlike the premarket approval (PMA) process, by law the 510(k) process, with some exceptions
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191 CONCLUSIONS AND RECOMMENDATIONS (discussed below), focuses solely on the determination of a device’s sub- stantial equivalence to a predicate device. According to the FDA and the Supreme Court, when the FDA finds a device substantially equivalent to a predicate device, it has done no more than find that the new device is as safe and effective as the predicate (OTA, 1984, p. 128).1 It is important to note that individual devices on the market before the enactment of the 1976 Medical Device Amendments (MDA)—the origin of all predicate devices for the 510(k) process—have never been systematically assessed to determine their safety and effectiveness (Finding 2-1). The FDA created advisory panels to assist in the device classification process. These panels reviewed information on the risks posed by types of devices, including the potential risks resulting from a failure of lack of effectiveness, and recommended into which class the device type should be placed, in order to provide a reasonable assurance of safety and effectiveness. Neither the panels nor the FDA itself undertook an assessment of the clinical safety or effectiveness of individual devices during the original classification process. Because the preamendment device to which equivalence was established was not itself reviewed for safety or effectiveness, the committee found that clearance of a 510(k) submission was not a determination that the cleared device was safe or effective (Finding 4-1). Under the Safe Medical Devices Act of 1990, the FDA is permitted to require evidence of safety and effectiveness, including clinical studies, when it is necessary for determining whether a difference in technologic charac- teristics between a new device and its predicate renders the new device less safe or effective than the predicate or raises different questions of safety and effectiveness from the predicate. If, despite the change in technologic characteristics, the new device is as safe and effective as the predicate, it will be found substantially equivalent. Nearly all 510(k) submissions for devices that have new technologic characteristics receive a determination of substantial equivalence. About 15% of Class II and Class III 510(k) submissions for which the FDA reached a determination of substantially equivalent or not substantially equivalent in FY 2005–2007 had new technologic characteristics (GAO, 2009a). Some 99.5% received a determination of substantially equivalent. The 510(k) clearance process has evolved from 1976 to the present through administrative and legislative changes, narrowing the array of is- sues that the FDA may consider in a 510(k) review, and limiting the type of evidence the FDA could require. Throughout the entire period, there has 1Memorandum Re: Internal Control Weaknesses in the Food and Drug Administration’s Medical Device 510(k) Review Process, from the HHS inspector general to the HHS assistant secretary for health (July 5, 1990) 1, fn. 1; Brief for the United States as Amicus Curiae Supporting Respondents/Cross-Petitioners 19-20, Medtronic, Inc. v. Lohr, 518 U.S. 470 (1996) (No. 95-754) (some internal citations omitted); Lohr, 518 U.S. at 493-94 (citations omitted).
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192 MEDICAL DEVICES AND THE PUBLIC’S HEALTH been a high frequency of finding of substantial equivalence (Finding 2-6). Furthermore, the gap in relative burdens on manufacturers between the 510(k) process and the PMA process created by the 1976 MDA has been maintained by administrative and legislative changes, which have encour- aged preferential use of the 510(k) process (Finding 2-7). Available Recall Data on 510(k)-Cleared Devices The committee explored FDA recalls of medical devices as a potential indicator of their safety and effectiveness. Proponents of the 510(k) clear- ance process have cited the low number of Class I recalls associated with 510(k)-cleared devices as an indication of the safety of devices on the mar- ket. (The FDA classifies recalls in reverse order of device classes. Class I re- calls denote the greatest immediate risk to the health, whereas Class I devices present the lowest inherent risk to health.) In contrast, consumer-protection advocates have cited several high-profile medical-device safety issues, some reported in the mass media, as evidence that premarket review via the 510(k) process is inadequate. They have expressed concern that the FDA’s ability to recall problematic medical devices cleared through the 510(k) process is insufficient (Bloomberg News, 2008; Harris, 2010a, 2010b; Hines et al., 2010; Meier, 2010; Mundy and Favole, 2009; Shuren, 2010; Stein, 2010; Zuckerman et al., 2011). Although the committee cites recall data in this report, it recognizes that using these data as an indicator of device safety and effectiveness has several shortcomings. The committee also recognizes that mass-media re- ports of problematic medical devices that were cleared through the 510(k) clearance process do not necessarily represent generalizable evidence about the soundness of the entire 510(k) program. The committee does not believe that there is a public-health crisis re- lated to unsafe or ineffective medical devices. The committee found that available postmarketing-surveillance data do not provide sufficient informa- tion about potential harm or lack of effectiveness to be a useful source of data about the safety and effectiveness of marketed devices (Finding 5-2). As noted in Finding 2-1, although the safety and effectiveness of preamend- ment Class II devices has not been systematically reviewed, their continued use in clinical practice provides at least a level of confidence in their safety and effectiveness.
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193 CONCLUSIONS AND RECOMMENDATIONS Does the 510(k) Clearance Process Provide a Reasonable Assurance of Safety and Effectiveness? The committee found that the 510(k) program lacks the statutory basis to make it a reliable premarket screen for safety and effectiveness of Class II medical devices. Therefore, the committee drew the following conclusion: Conclusion 7-1 The 510(k) clearance process is not intended to evaluate the safety and effectiveness of medical devices with some exceptions. The 510(k) process cannot be transformed into a pre- market evaluation of safety and effectiveness as long as the standard for clearance is substantial equivalence to any previously cleared device. The committee is not suggesting that all, many, or even any medical devices cleared through the 510(k) clearance process and currently on the market are unsafe or ineffective. Rather, the committee found that the available information is insufficient to support highly confident conclusions about the safety and effectiveness of 510(k)-cleared medical devices in clini- cal use. As elaborated on below, the committee is concerned by the lack of information-gathering efforts to identify potential safety and effectiveness problems with devices and by the ineffectiveness of the regulatory system to respond to problems if they are identified (Finding 3-2). FACILITATING INNOVATION IN SUPPORT OF PUBLIC HEALTH As discussed in Chapter 6, views diverge on what constitutes innova- tion in medical devices. The committee agreed on a definition of innovation to assess whether the current 510(k) clearance process optimally protects patients and promotes innovation in support of public health. The commit- tee believes that given the broad interpretation of the term it should define innovation not simply as a change but as a favorable change in the context of public health. The committee also believes that given the complexity of the process of innovation and the iterative and combinatorial nature of the process a broad definition would be more accurate than one that sought to create a list of specific attributes. The committee defined innovation broadly as improving the quality of, efficiency of, or access to health care. To assess how innovation is affected by medical-device regulation, the committee studied the legislative history and implementation of the 510(k) process and findings from the medical-device industry about the effect of the 510(k) process on innovation. The committee found that the 510(k) clearance process was not designed to reward, recognize, or encourage in- novation. At most, promotion of innovation was a byproduct of a process that, by minimizing unnecessary regulatory burdens, facilitated the entry
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194 MEDICAL DEVICES AND THE PUBLIC’S HEALTH into the market of new devices that do not raise novel questions of safety or effectiveness (Finding 2-4). In reducing regulatory burdens and providing additional resources to allow for timely review, the changes in the original legislation over the past 35 years have neither forced nor rewarded in- novation. Although it may be argued that such changes may improve the likelihood of innovation, it remains unclear, and the committee argues that it is indeterminable given current data, whether the legislative changes have promoted innovation. The 510(k) clearance process is generally more economical, faster, and less burdensome than the PMA process for both industry and the FDA (Finding 3-3). Substantially fewer postmarket controls apply to 510(k)- cleared devices than to PMA devices. Since the implementation of the MDA of 1976, which created both programs, there has been a substantial difference between the 510(k) process and the PMA process in premarket requirements. The committee found that over the past 35 years legislative and administrative changes in the 510(k) program have maintained that gap in requirements between the 510(k) and PMA programs. The disparity in program requirements, costs, and postmarket requirements encourages preferential use of the 510(k) process (Finding 2-7). Although the 510(k) clearance process offers a less burdensome pathway to market, the increas- ing complexity of devices is challenging the capabilities of this process (Findings 6-1, 6-2, 6-3, and 6-4). The committee believes that a regulatory pathway based on demonstrating substantial equivalence to predicate de- vices is not a rigorous scientific means of adapting to new and increasingly complex types of technology. Several assessments of the 510(k) program conclude that the FDA’s implementation of the program, not the underlying process itself, has stifled innovation because of a lack of transparency and predictability, which has led to an adverse effect on venture-capital investment in future medical-device development (Finding 6-5). Typical measures used in those assessments are the ease of premarket review and relative speed to market compared with the European Union premarket process (Ernst and Young, 2009; Lewin Group, 2010; Makower et al., 2010; MDMA and NVCA, 2009; PwC and BIOCOM, 2010). The committee, however, does not believe that such factors as ease of premarket review and relative speed to market are surrogates for innovation. The FDA has procedures to develop, adopt, and implement guidance and standards. It is persistently hindered, however, in fully developing these materials by a lack of or limitations in human, fiscal, and technologic re- sources and capabilities (Finding 3-4). Confusion regarding key regulatory phrases (for example, intended use and indications for use) has created uncertainty about the decision-making process (Finding 4-3). The process also is restricted in how it evaluates devices in that it currently does not
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195 CONCLUSIONS AND RECOMMENDATIONS recognize the distinction between devices cleared as tools and devices cleared for specific clinical applications (Finding 4-4). Those factors create confu- sion regarding the types of questions asked by reviewers and the types of information needed in premarket submissions. In its Task Force on the Utilization of Science in Regulatory Decision Making Preliminary Report and Recommendations, CDRH identified sev- eral institutional, structural, and resource concerns regarding the timely incorporation of new science in premarket review (FDA, 2010b). The report found that the CDRH has not yet articulated a business process to be followed across the Center for evaluating new scientific information and determining when that information warrants certain types of action, such as a change in premarket evidentiary expectations. The Utilization of Science report also states that CDRH finds it chal- lenging to communicate changes in regulatory thinking both within the agency and externally in response to new information and that this challenge affects all stakeholders. Industry representatives have expressed concern about the increasingly required use of clinical data in the 510(k) review. The committee’s evaluation found that the FDA has provided inconsistent guidance in determining the need for clinical data, the type of data, and the manner in which data, if available, should be integrated into the decision- making process (Finding 4-8). The lack of clear guidance affects the timeli- ness and consistency of 510(k) device submissions provided by industry and the ability of reviewers to evaluate them. Does the 510(k) Clearance Process Promote Innovation in Support of Public Health? On the basis of the above findings, the committee was unable to de- termine whether the 510(k) clearance process is facilitating or inhibiting innovation. Therefore, the committee concludes as follows: Conclusion 7-2 Information that would allow an understanding of the extent to which the 510(k) clearance process facilitates or inhibits innovation does not exist. The committee believes that although the regulatory process can facili- tate innovation that improves public health by making safe and effective Class II medical devices available to consumers in a timely manner, the FDA should not be the arbitrator of what constitutes innovation, nor should it seek to channel device development and premarket review toward agency- determined public-health priorities. In the committee’s opinion, the FDA’s
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196 MEDICAL DEVICES AND THE PUBLIC’S HEALTH role in facilitating innovation in Class II medical devices through premarket review should be to create a regulatory framework that sets appropriate thresholds for bringing products to the market. The thresholds should be stringent enough to satisfy the agency’s objective of ensuring that marketed medical devices will be safe and effective throughout their life cycles but realistic enough to permit timely entry of new devices that may offer im- provements over already marketed devices. Rather than be charged with promoting innovation, the committee believes that the FDA should seek to facilitate it, ensuring that the premarket review of Class II devices does not needlessly inhibit innovation. RECOMMENDATIONS On the basis of the above conclusions, the committee offers the follow- ing recommendations aimed at improving regulation of Class II medical devices. Recommendation 7-1 The Food and Drug Administration should obtain adequate information to inform the design of a new medical- device regulatory framework for Class II devices so that the current 510(k) process, in which the standard for clearance is substantial equivalence to previously cleared devices, can be replaced with an integrated premarket and postmarket regulatory framework that effectively provides a reasonable assurance of safety and effective- ness throughout the device life cycle. Once adequate information is available to design an appropriate medical-device regulatory framework, Congress should enact legislation to do so. The committee believes that a move away from the 510(k) clear- ance process should occur as soon as reasonably possible but recognizes that it will take time to obtain the information needed to design the new framework. It is essential that the new regulatory framework be based on sound sci- ence. The committee does not believe that available information is adequate to inform the design of an appropriate framework. Nor does the committee believe that the new framework should be developed in isolation from other components of the FDA’s medical-device regulatory system. In developing the new framework for Class II devices, the efficiency, cost, and effective- ness of the PMA process should be evaluated. The FDA should carefully consider what types of evidence are necessary to demonstrate a reasonable assurance of safety and effectiveness in the new framework. It is beyond the committee’s scope of work to detail those types of evidence. The committee believes that it may be possible for the performance of comparative devices
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197 CONCLUSIONS AND RECOMMENDATIONS to be a component of the evidentiary materials supporting a claim of safety and effectiveness of Class II devices. The FDA should be clear that its role in facilitating innovation in medi- cal devices is to develop regulatory thresholds that are rigorous enough to satisfy the agency’s primary objective of ensuring that marketed medical devices will be safe and effective throughout their life cycles but realistic enough to permit timely entry of new devices into the market. On the basis of its findings, the committee identified several topics to which the FDA should give particular consideration as it develops a new framework. A number of existing and emerging technologies (for example, combination products, software, nanotechnology, and medical robotics) merit detailed thought as part the development of the new framework. The FDA should consider integrating some elements of the quality-system regulations, especially those related to design controls and product-release criteria, into the premarket review process of the new framework to demon- strate that devices will perform as represented by their manufacturers. The FDA should also consider, as part of the new framework, including a more extensive review of device labeling and a system to track labeling changes. A comprehensive review of the successes and problems of device regula- tion over the past 35 years would better inform the FDA and Congress as to whether and how to change the overall regulatory structure for devices. Finally, medical-device regulatory systems in other countries and jurisdic- tions should be evaluated to determine whether components of those sys- tems could inform the design of the new regulatory framework in the United States. The committee notes that medical-device regulatory systems in other countries that have robust medical-device markets do not use substantial equivalence to predicates as the standard for approval for marketing (Find- ing 6-8). The committee urges the FDA to create a regulatory framework that more closely matches the ideal regulatory framework outlined by the com- mittee in Chapter 1. The attributes of this regulatory framework are as follows. They are not presented in any priority order. • T he process should be based on sound science. • T he process should be clear, predictable, straightforward, and fair. • T he process should be self-sustaining and self-improving. • T he process should facilitate innovation that improves public health by making medical devices available in a timely manner and ensuring their safety and effectiveness throughout their life cycle. • he process should apply relevant and appropriate regulatory au- T thorities and standards throughout the life cycle to ensure safety and effectiveness. • he process should be risk-based. T
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198 MEDICAL DEVICES AND THE PUBLIC’S HEALTH FDA staff at all levels, the medical-device industry, consumers, health- care providers, payers, and Congress must play a role in the development of the proposed regulatory framework. The committee does not believe that further investment in the 510(k) process is a wise use of the FDA’s scarce resources and is not recommending specific changes in the 510(k) clearance process itself. Instead, it believes that the FDA’s resources would be put to better use in addressing problems with other components of the medical-device regulatory framework and with the FDA’s decision-making processes and obtaining information needed to develop a new framework for Class II medical devices. The committee’s recommendations for accomplishing those goals are detailed below. The committee recognizes that scarce resources in the FDA could affect its ability to implement these recommendations. Therefore, it has directed the recom- mendations toward activities that are useful in both the short term and the long term and that conserve scarce resources. The committee recommends that the FDA promptly implement Recom- mendations 7-2 to 7-8, found below. The committee believes that following these recommendations will allow the FDA to • evelop the information base on which to establish the new regula- D tory framework. • ddress problems with postmarketing surveillance and with use of A postmarket regulatory authorities. • evelop and implement a continuous quality-improvement system D in CDRH. Postmarketing Surveillance As stated repeatedly in the report, the 510(k) clearance process is not a stand-alone program but a component of the larger medical-device regula- tory framework. As part of that framework, the 510(k) program depends on the effectiveness of other regulatory components. The committee found weakness in postmarketing surveillance of medical devices (Findings 4-5, 4-6, 5-1 to 5-7, and 6-7). The committee found evidence that the FDA’s postmarketing surveil- lance systems, as well as other postmarket activities, often do not provide sufficient information about potential harm or lack of effectiveness of marketed devices (Findings 4-5 and 5-2). The FDA’s active postmarketing surveillance programs, such as MedSun and MD EpiNet, have potential but will require stable, adequate resources and resolution of various technical issues to achieve their full promise (Finding 5-5). The FDA is including medi- cal devices in the Sentinel Initiative; additional investment will be needed to develop a rich source of clinical data on medical devices. The FDA’s device
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199 CONCLUSIONS AND RECOMMENDATIONS postmarketing surveillance programs have been adversely affected by the instability of the agency’s congressional financing. Moreover, user fees can be used only for premarket activities (Finding 2-8). Non-FDA postmarket- ing surveillance activities, such as privately funded device registries, are potentially important sources of performance information, but currently only selected device types are studied, and the lack of standardization in how information is collected and reported persists (Findings 5-6 and 5-7). Finally, there is little collaboration in collection of postmarketing surveil- lance data among the FDA, healthcare facilities, healthcare providers, the medical-device industry, professional societies, payers, and patient-advocacy groups (Finding 6-7). The inadequate postmarketing surveillance systems—both those in the FDA and those which are privately funded—and the resulting lack of useful, consistent, and reliable data make it impossible to draw confident conclusions about the performance of medical devices now on the market. Recommendation 7-2 The Food and Drug Administration should develop and implement a comprehensive strategy to collect, analyze, and act on medical-device postmarket performance information. The FDA should give high priority to postmarketing surveillance be- cause it is an invaluable investment in short-term and long-term medical- device safety oversight and assessment of device effectiveness. As discussed in Chapter 5 of this report, the committee found that there was no long-term strategy in the FDA to address the effectiveness of medical-device post- marketing surveillance. The committee recommends that the FDA develop a postmarketing surveillance strategy to meet the following objectives: provide performance information for use in the premarket review process, inform the development and use of postmarketing tools (that is, general and special controls) to better manage the risk-benefit ratio throughout the life cycle of devices, and inform the design of a new regulatory framework. To meet those objectives, the FDA should • xplore how to better understand potential device risks better with E existing postmarket tools, such as device tracking and Section 522 surveillance studies. • xpand collaborative relationships with existing non-FDA medical- E device data sources and encourage standardization of processes and systems to increase efficiency and the ability of all parties to use the data. • nstitutionalize integration of premarket and postmarket data I systems.
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200 MEDICAL DEVICES AND THE PUBLIC’S HEALTH • dentify methods for learning from independent clinical research I reported in the peer-reviewed literature on poor or adverse health outcomes related to devices that may warrant FDA action. • evise its strategy to communicate more effectively with consumers, R providers, and the public about problems with the performance of medical devices. The committee acknowledges that the traditional administrative and clinical data sources used for surveillance of drugs may not be appropri- ate for surveillance of medical devices, particularly surveillance of Class II devices. Device surveillance will probably require other data sources, such as unique device identifiers (discussed in Chapter 5). Congress should support the capacity of CDRH’s postmarketing surveil- lance programs by providing stable and adequate funding. Postmarket Regulatory Authorities When the FDA discovers violations of the law or products that pose unacceptable risks to consumers, it has a wide variety of authorities (or tools) available to remedy the situation and to sanction the violators. The committee found that the agency uses these authorities sparingly (Findings 3-1 and 3-2). Although the committee identified the procedural require- ments that the FDA must fulfill to exercise the authorities, the requirements do not in themselves appear to explain CDRH’s perception that there are “important limitations” on the use of postmarket tools. Recommendation 7-3 The Food and Drug Administration should review its postmarket regulatory authorities for medical devices to identify existing limitations on their use and to determine how the limitations can be addressed. The appropriate use of postmarket regulatory authorities is an essential component of a successful medical-device regulatory program. The FDA should analyze barriers to efficient and effective use of these authorities and identify means to mitigate the barriers. It is especially important that the FDA be able to use the authorities, when needed, because a 510(k) decision made by the FDA establishes a new predicate device that is legally binding unless and until the agency has rescinded the decision or has barred the device covered by that decision from the market through other legal actions (Finding 2-3). If required, Congress should pass legislation to remove unnecessary barriers to the FDA’s use of postmarket regulatory authorities.
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201 CONCLUSIONS AND RECOMMENDATIONS A Modified De Novo Process The committee believes that the de novo process offers a potential basis of a better regulatory model for premarket review of Class II devices. In its current state, however, the de novo process is time-consuming and difficult for both the FDA and manufacturers to navigate (Finding 4-9). Recommendation 7-4 The Food and Drug Administration should investigate the viability of a modified de novo process as a mecha- nism for evaluating the safety and effectiveness of Class II devices. A pilot program of a modified de novo process would allow the FDA to determine the feasibility of the modified process as a replacement for the 510(k) clearance process. The 1976 MDA states that general controls alone are not sufficient to ensure the safety and effectiveness of Class II devices. Therefore, as part of a modified de novo process, the FDA should explore ways to expedite development of special controls, develop guidances, and adopt standards for devices. The agency also should consider expanded use of external expertise and preinvestigational device exemption meetings with submitters and use of conditional clearances for devices on which there is little premarket performance information (such as a clearance conditioned on postmarketing surveillance or use of registries). The success of the modified de novo process will depend on CDRH’s ability to develop a rich database on its processes and performance. There- fore, it is imperative that CDRH develop a comprehensive information- technology strategy based on an assessment of program needs and practices. A Continuous Quality-Improvement Program The committee’s assessment of the 510(k) clearance process showed that CDRH’s operations lack a continuous quality-assurance process (Finding 3-5). CDRH’s Task Force on the Utilization of Science in Regulatory Deci- sion Making found that the center did not have a process for addressing the use of new types of scientific information in regulating medical devices (FDA, 2010b). Lack of such a process prevents CDRH from effectively ad- dressing new issues as they arise and from developing a long-term vision of the center and its mission. For example, the Government Accountability Office found that CDRH does not have a comprehensive information- technology strategic plan that would allow it to meet its needs as it modern- izes (GAO, 2009b). Recommendation 7-5 The Food and Drug Administration should de- velop and implement a program of continuous quality-improvement to track regulatory decisions on medical devices, identify potential
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202 MEDICAL DEVICES AND THE PUBLIC’S HEALTH process improvements in the medical device regulatory framework, and address emerging issues that affect decision-making. Throughout the report, the committee identifies evidence that the inad- equate information technology and management infrastructure in CDRH af- fects not only the 510(k) program but also the center’s other programs. For example, because data systems in the FDA are inadequate, the agency does not have the ability to trace the history of 510(k) decisions (Finding 4-2). Those 510(k) clearances are legally binding on CDRH for making future decisions about devices going through the 510(k) clearance process. Thus, any unsafe or ineffective devices are embedded in the system and as both a legal and a practical matter may be used as predicates for new products until they are removed from the market. Removing those devices from the market may be difficult because there is no systematic way to identify them. By developing a business model grounded in continuous quality-improvement, CDRH will be able to identify problems and develop the information and capacity to address them in a data-driven, transparent manner. Facilitating Innovation in the Medical-Device Industry As stated above, the committee believes that the FDA’s role in facilitat- ing innovation with respect to Class II devices is to create and enforce a regu- latory framework where the threshold to market provides reasonable assur- ance that medical devices are safe and effective throughout their life cycle while permitting timely entry of new devices that may offer improvements over already marketed devices. The committee did not find assessments of how much and in what way (that is, facilitating or inhibiting) innovation is influenced by the 510(k) clearance process (Finding 6-6). Recommendation 7-6 The Food and Drug Administration should commission an assessment to determine the effect of its regulatory process for Class II devices on facilitating or inhibiting innovation in the medical-device industry. The recommended study should include various ways to measure in- novation beyond “time to market” or the number of devices of a particular type on the market and instead focus on a broader understanding of the relationship among regulation, innovation, and patient health and safety throughout the device life cycle. There should be analysis of how incremen- tal changes in existing devices affect clinical use, safety, and effectiveness; characterization of research and development costs for truly innovative technologies that enhance healthcare quality, efficiency, or access; estimates of the effects of government interventions (for example, subsidies, mar-
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203 CONCLUSIONS AND RECOMMENDATIONS ket exclusivity, and research support); and description of the current and foreseeable relationship between FDA clearance or approval and payers’ willingness to reimburse for devices. Software Because of software’s important differences from hardware (as discussed in Chapter 6), the FDA should develop a better understanding of the roles that software plays in medical devices, analyze their potential effects on the safety and effectiveness of the devices, and insist on evidence-based proce- dures that ensure device safety and effectiveness. The committee believes that the FDA should review and update its guidance on software validation. Updating the guidance is important given the increasing use of software in devices and as devices (for example, medical device data systems), the integration in medical devices of commercial software not intended for use in them, the increasing uncertainty introduced by device complexity, and potentially unsafe interactions with other software systems. Reliance on “best practices” is no longer sufficient, particularly when best-practice recommendations often lag behind rapid change in software innovation. The FDA should commission an independent study focused on addressing these questions and concerns about software in medical devices. The study should include not only an analysis of potential system problems introduced by software but also recommendations about how the FDA can evaluate a device’s software with respect to safety, dependability, security, reliability, and privacy. As suggested in a National Research Council study about ensuring software dependability (NRC, 2007), the FDA should develop an evidence- based approach for use by the medical-device industry to support its claims of safety and effectiveness. Thus, one output of the present committee’s recommended study should be evidential guidance to industry: What should be reported to demonstrate safety and dependability? At present, most available information about safety and effectiveness of devices relies only on recall data; there is little specificity about the contribu - tion of software to failures that lead to recalls. Thus, it is not always possible to understand the particular contribution of software to device quality and function; neither is it clear what oversight is needed in the premarket review process. Moreover, because software engineers learn as much from failure as from success, the scope of device-related reporting should be broadened to include not only information about software-related device failures but also descriptions of near-failures: What happened, why it happened, and what can be done to prevent such problems in the future? The information gained from such surveillance can inform the design and development of new or modified software and the review of premarket submissions.
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204 MEDICAL DEVICES AND THE PUBLIC’S HEALTH Recommendation 7-7 The Food and Drug Administration should develop procedures that ensure the safety and effectiveness of soft- ware used in devices, software used as devices, and software used as a tool in producing devices. Preamendment 510(k)-Eligible Class III Devices After 35 years, the FDA has not completed the task of calling for PMAs for or reclassifying preamendment Class III device types. Until the FDA completes that task, those devices are allowed to enter the market through the 510(k) clearance process (Finding 4-7). Congress in 1990 directed the FDA to complete that task in a timely manner.2 Currently 25 device types remain eligible to enter the market through the 510(k) process. The FDA has begun a five-step process to require PMAs or to reclassify those device types to a lower class (GAO, 2011). As of April 2011, the FDA has assessed the risks and benefits associated with 21 device types (step 2 of the process) and has received and reviewed public comments on 5 device types (step 4 of the process). The agency has issued a final rule for one of the 26 device types (FDA, 2011). The committee recognizes the resource constraints that have prolonged this process, but it nevertheless urges the FDA to give high priority to completing this task. Recommendation 7-8 The Food and Drug Administration should promptly call for PMA applications for or reclassify Class III de- vices that remain eligible for 510(k) clearance. REFERENCES Bloomberg News. 2008. Surgical mesh tied to complications. The New York Times, 10/22/2008. Ernst and Young. 2009. Pulse of the industry: Medical technology report. FDA (Food and Drug Administration). 2010a. CDRH preliminary internal evaluations— Volume I: 510(k) working group preliminary report and recommendations. Silver Spring, MD: Food and Drug Administration. ———. 2010b. CDRH preliminary internal evaluations—Volume II: Task force on the utiliza- tion of science in regulatory decision making preliminary report and recommendations. Silver Spring, MD: Food and Drug Administration. ———. 2011. Guidance for industry and FDA staff—Class II special controls guidance document: Topical Oxygen Chamber for Extremities. http://www.fda.gov/downloads/ MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM252364.pdf (accessed 08/3/2011). GAO (Government Accountability Office). 2009a. FDA should take steps to ensure that high-risk device types are approved through the most stringent premarket review process (GAO-09-190). Washington, DC: Government Accountability Office. 2SMDA, Pub. L. No. 101-629, 104 Stat. 4511.
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205 CONCLUSIONS AND RECOMMENDATIONS ———. 2009b. Information technology: FDA needs to establish key plans and processes for guiding systems modernization efforts (GAO-09-523). Washington, DC: Government Accountability Office. ———. 2011. Testimony before the Special Committee on Aging, U.S. Senate. Medical devices: FDA’s premarket review and postmarket safety efforts (GAO-11-556T). 04/13/2011. Harris, G. 2010a. FDA vows to revoke approval of device. The New York Times, 10/14/2010. ———. 2010b. U.S. inaction lets look-alike tubes kill patients. The New York Times, 08/21/2010. Hines, J. Z., P. Lurie, E. Yu, and S. Wolfe. 2010. Left to their own devices: Breakdowns in United States medical device premarket review. PLoS Medicine 7(7):e1000280. Lewin Group. 2010. State economic impact of the medical technology industry. Washington, DC: AdvaMed. Makower, J., A. Meer, and L. Denend. 2010. FDA impact on U.S. medical technology innova- tion: A survey of over 200 medical technology companies. Mountain View, CA. MDMA (Medical Device Manufacturers Association) and NVCA (National Venture Capital Association). 2009. Medical technology and venture capital: A fruitful yet fragile ecosys- tem. Washington, DC Meier, B. 2010. The implants loophole. The New York Times, 12/17/2010, B1. Mundy, A., and J. A. Favole. 2009. FDA rips approval of medical device. The Wall Street Journal, 09/25/2009. NRC (National Research Council). 2007. Software for dependable systems: Sufficient evidence? Washington, DC: The National Academies Press. OTA (Office of Technology Assessment). 1984. Federal policies and the medical devices indus- try. Washington, DC: Congress of the United States, Office of Technology Assessment. PwC (PricewaterhouseCoopers) and BIOCOM. 2010. Improving America’s health: A survey of the working relationship between the life sciences industry and FDA. San Diego. Shuren, J. 2010. How to reduce tube mix-ups in hospitals. The New York Times, 08/26/2010. Stein, R. 2010. FDA admits mistake with knee device. The Washington Post, 10/19/2010. Zuckerman, D. M., P. Brown, and S. E. Nissen. 2011. Medical device recalls and the FDA approval process. Archives of Internal Medicine 171(11):1006-1011.
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