Portfolio Media. Inc. 860 Broadway, 6th Floor New York, NY 10003 www.law360.com Phone: +1 646 783 7100 Fax: +1 646 783 7161 customerservice@law360.com Overhauling The 510(k) Process Law360, New York (August 19, 2011) -- On July 29, 2011, the Institute of Medicine (IOM) released the long-awaited report of its Committee on the Public Health Effectiveness of the FDA 510(k) Clearance Process (IOM Committee). The report recommended replacing the current 510(k) process with an integrated premarket and postmarket regulatory framework, which would likely result in a longer and more expensive pathway to market for manufacturers of moderate-risk medical devices. The IOM Committee s Report (IOM Report) assessed the 510(k) process and made a host of recommendations. Notably, the IOM Report recommends that the 510(k) clearance process which considers whether a medical device is substantially equivalent to a previously cleared device be replaced with an integrated premarket and postmarket regulatory framework focused on whether a device is safe and effective throughout its lifecycle. Although this recommendation is unlikely to be adopted, the IOM Report contains extensive commentary on the current 510(k) program and is likely to inform the U.S. Food and Drug Administration's ongoing review of the program. Background of the IOM Report The IOM Report results from FDA s comprehensive assessment of the 510(k) process in response to concerns regarding the program. Industry members are concerned that it stifles innovation, delays promising technologies and imposes excessive burdens on industry, while consumers and health care professional groups worry that the program does not adequately assure safety and effectiveness. FDA commissioned the IOM to assess whether the 510(k) process sufficiently protects patients and promotes public health, by answering two principal questions: 1) Does the current 510(k) process optimally protect patients and promote innovation in support of public health? 2) If not, what legislative, regulatory or administrative changes are recommended to optimally achieve the goals of the 510(k) process? The IOM Committee s review has not been without controversy: Industry representatives have questioned the fairness of the IOM Committee s membership and have challenged the FDA s ability to consider the IOM Report s recommendations. Summary of the IOM Report The IOM Committee evaluated the 510(k) process and other factors it considered relevant. Key observations and findings are summarized below. Legislative Framework of the 510(k) System
The 510(k) process enacted by the Medical Device Amendments of 1976 (MDA) and subsequent amendments assesses whether new Class II medical devices are substantially equivalent to existing (predicate) devices, rather than whether new devices are safe and effective. The MDA required classification of pre-amendment medical devices into Class I, II or III, based on the risks they present. Pre-amendment devices placed into Class I or II were not systematically reviewed for safety or effectiveness. Nonetheless, Class II devices are legally binding as predicates unless FDA rescinds a clearance or bars a device. The ongoing use of pre-amendment Class II medical devices in clinical practice provides a level of confidence as to their safety and effectiveness. The 510(k) process was not designed to reward, recognize or encourage innovation. Medical Device Regulation The FDA has tools for addressing safety risks in marketed devices, but it has not used them extensively. Although the FDA faces some procedural burdens in using them, those burdens do not appear to be the cause of the FDA s sparse use of these tools. The FDA s Center for Devices and Radiological Health (CDRH) also is challenged by limited human, fiscal, and technologic resources and capabilities. CDRH lacks an adequate quality assurance mechanism for the 510(k) process. Analysis of the 510(k) Clearance Process The terms intended use and indications for use which are separate, key concepts in the 510(k) clearance process are poorly defined and are susceptible to varying interpretations that lead to inconsistency in decision-making and create confusion. The FDA cannot refuse to clear a device based on potential unsafe or ineffective offlabel uses, even if they are foreseeable. Manufacturers could conceivably describe lower-risk intended uses in their 510(k) submissions, in order to avoid describing higher-risk potential uses that would trigger the more burdensome premarket approval process for higher-risk medical devices. Limits on the FDA s capacity to collect data and conduct postmarketing surveillance of devices adversely affects its ability to identify off-label uses and resulting adverse events. The FDA does not have a consistent approach for determining the need for clinical data, the type of such data, and the manner in which such data, if available, are integrated into the decision-making process.
The FDA s de novo process was intended to streamline the marketing clearance process for novel low- or moderate-risk devices, but it has proven to be cumbersome and lengthy for some Class II devices and has not met its potential as an alternative regulatory pathway. Postmarketing Surveillance, Compliance and Enforcement The FDA s postmarketing surveillance program is inadequate, in part because it depends on third parties to identify, collect and report data. The program s weaknesses prevent the FDA from effectively analyzing the safety and effectiveness of marketed medical devices. Data collected through FDA s current postmarketing surveillance system are not systematically integrated into the premarket review process. The FDA has used only sparingly its postmarketing surveillance tools. Some FDA postmarketing surveillance programs are scientifically promising, but they have not fulfilled their potential because of technical issues and inadequate resources. External Factors Affecting U.S. Medical Device Regulation Since the MDA s enactment, the number of types of medical devices has grown significantly, medical device technology has evolved rapidly and devices have become increasingly complex. Manufacturers increasingly use software in devices, as devices and as tools for producing devices. Although software offers many benefits, it has been linked to an increasing number of recalls and poses particular challenges, which the regulatory process must take into account. The IOM Committee defined innovation as improving the quality of, efficiency of, or access to healthcare. Currently available data do not allow an assessment of whether changes in the 510(k) process have promoted innovation in balance with public health rather than at its expense. Industry-funded assessments of the 510(k) process report that a lack of predictability and transparency has an adverse effect on venture capital investment. FDA and medical device manufacturers operate in the wider context of international markets and regulatory structures. IOM Committee Conclusions and Recommendations The IOM Committee came to two major conclusions: The 510(k) clearance process is not intended to evaluate the safety and
effectiveness of medical devices with some exceptions [and] cannot be transformed into a premarket evaluation of safety and effectiveness as long as the standard for clearance is substantial equivalence to any previously cleared device. Information that would allow an understanding of the extent to which the 510(k) clearance process either facilitates or inhibits innovation does not exist. The IOM Committee also proposed eight recommendations to improve regulation of Class II medical devices. The first is the most significant: "[The FDA] should obtain adequate information to inform the design of a new medicaldevice regulatory framework for Class II devices so that the current 510(k) process can be replaced with an integrated premarket and postmarket regulatory framework that effectively provides a reasonable assurance of safety and effectiveness throughout the device lifecycle. Once adequate information is available to design an appropriate medicaldevice regulatory framework, Congress should enact legislation to do so." Despite recommending this sweeping change, the IOM Committee provided only minimal guidance as to the shape of a prospective regulatory framework, suggesting that the framework should consider existing and emerging technologies, integrate elements of the FDA s Quality System Regulation for medical devices and include more extensive review of device-labeling and a system to track labeling changes. The IOM Committee recognized that its proposal would take time to implement but suggested that a move away from the 510(k) clearance process should occur as soon as reasonably possible. The IOM Committee declined to recommend specific changes in the 510(k) clearance process itself, finding that further investment in the process is not a wise use of the FDA s scarce resources. Instead, the IOM Committee s additional recommendations included: The FDA should develop and implement a comprehensive strategy to collect, analyze and act on postmarket performance information, in order to inform the premarket review process, the development and use of postmarketing tools and the design of a new regulatory framework. The FDA should review its postmarket regulatory authorities to identify existing limitations and determine how to address those limitations, particularly because clearances are legally binding unless the FDA rescinds a clearance or bars a device. The FDA should investigate the viability of a modified de novo process as a mechanism for evaluating the safety and effectiveness of Class II devices and implement a pilot program to determine whether a modified de novo process is a feasible replacement for the current 510(k) process. The FDA should develop and implement a quality-assurance process to track device regulatory decisions, identify potential improvements in the regulatory framework and address emerging issues. The FDA should commission an assessment to determine the effect of the 510(k)
process on facilitating or inhibiting innovation. The assessment should focus on the relationship among regulation, innovation, and patient health and safety, rather than time to market or the number of marketed devices of a particular type. The FDA should develop procedures to ensure the safety and effectiveness of software, including use of an assurance case approach for demonstrating the safety and effectiveness of device-related software. The FDA should promptly call for premarket approval applications for, or reclassify Class III devices that remain eligible for, 510(k) clearance. Potential Impact on Industry of IOM Conclusions and Recommendations While the IOM Report calls for overhauling the 510(k) process, this recommendation is unlikely to be implemented given the lack of consensus among industry, regulatory officials and other stakeholders on whether such sweeping changes are necessary, much less on what regulatory framework should take its place. The FDA and numerous medical device manufacturers and industry groups have announced reservations about this recommendation. Although industry representatives recognize that the 510(k) process could be improved, they believe it has encouraged innovation and facilitated the marketing of new products, while adequately ensuring their safety and effectiveness. The FDA and industry representatives also believe that safety and effectiveness in the 510 (k) context should be judged based on the entire applicable regulatory context (including quality system and current good manufacturing practices requirements, special controls and postmarketing enforcement), rather than just the 510(k) review process. Even if the IOM Committee s main recommendation is not implemented, the IOM Report offers a detailed evaluation of the current 510(k) program and highlights areas for potential reform, many of which are already under consideration by the FDA as part of its comprehensive assessment of the program. The IOM Report coupled with industry representatives support for certain of its recommendations is likely to increase FDA and congressional focus on the following issues: Safety and Effectiveness CDRH currently is considering proposals to (1) create a Class IIb of medical devices for which clinical, marketing or other information is required to support a 510(k) submission; (2) define CDRH s authority to rescind 510(k) clearances; and (3) clarify when a device should no longer be used as a predicate. If adopted, these recommendations would increase CDRH s focus on the safety and effectiveness of Class II devices; they therefore may receive additional attention in light of the IOM Committee s conclusion that the current process does not evaluate safety and effectiveness. Although disagreeing with this conclusion, some industry representatives have indicated that the process may benefit from, for example, greater differentiation among Class II products, which would allow CDRH to tailor its review protocols to better reflect risks associated with different device types. Innovation
The IOM Committee concludes that current data do not permit an assessment of the 510 (k) program s effect on innovation, and recommends that the FDA commission such an assessment. This assessment could spur efforts to make the process more transparent, easier to navigate and more focused on encouraging innovative devices. FDA representatives and IOM Committee members have confirmed their desire not to chill innovation as a result of changes to the 510(k) process. Postmarketing Surveillance and Authorities CDRH currently is considering a recommendation to seek greater authorities to require postmarket surveillance studies as a condition of clearance for certain devices. The IOM Report encourages the FDA to expand its use of current postmarketing tools as well as reexamine the limitations on its postmarket regulatory authorities to address safety issues involving marketed devices. If the FDA heeds the IOM Committee s suggestions, it may increase its use of current postmarketing surveillance tools, seek additional postmarketing tools and expand its use of judicial and administrative enforcement powers. All of these would result in greater costs and burdens on medical device manufacturers, health care professionals and patients. On the other hand, if a strengthened postmarketing surveillance and enforcement program could be coupled with less onerous initial 510(k) clearance requirements, the overall process might be more effective in promoting innovation while adequately protecting patient health and safety. De Novo Process The IOM Committee recommends that CDRH pursue a modified de novo process and consider expanded use of external expertise, pre-investigational device exemption meetings and conditional clearances. CDRH plans to release a draft guidance to streamline the de novo process by Sept. 30, 2011. Although that guidance is unlikely to address all of the IOM Committee s suggestions, some may find their way into CDRH s final guidance. Continued focus on the de novo process appears likely, and improvements may make it a faster and more cost-effective pathway for medical devices to reach the market. Software The IOM Report recommends that the FDA change its current processes for evaluating software, including by using assurance cases for software validation evidence. CDRH is currently soliciting public input on the use of assurance cases in 510(k) submissions and developing a pilot program. The IOM Committee s recommendation may inform CDRH s consideration and, on a broader level, may lead the FDA to reexamine its approach to software evaluation. While this could make the 510(k) process better suited to software and better able to ensure its safety and effectiveness, it also could force software manufacturers to comply with new, and perhaps more burdensome, requirements. Next Steps in FDA s 510(k) Review Process CDRH has opened a public docket to receive comments on the IOM Report until Sept. 30, 2011, and announced it will hold a public meeting on Sept. 16, 2011 to discuss the report s recommendations. The FDA has indicated that it will provide a response to the IOM Report by the end of October 2011. --By John Bentivoglio, Jennifer Bragg, Nicole Grimm and Maya Florence, Skadden Arps
Slate Meagher & Flom LLP. John Bentivoglio and Jennifer Bragg are partners in the Washington, D.C., office of Skadden. Nicole Grimm is a counsel, and Maya Florence is an associate, in the firm's Washington office. The opinions expressed are those of the authors and do not necessarily reflect the views of the firm, its clients, or Portfolio Media, publisher of Law360. This article is for general information purposes and is not intended to be and should not be taken as legal advice. All Content 2003-2010, Portfolio Media, Inc.