The highly-anticipated Institute of Medicine (IOM) report, Medical Devices and the Public's Health: The FDA 510(k) Clearance Process at 35 Years,1 evaluating the 510(k) clearance process was released Friday morning to a substantial amount of controversy. As described in more detail below, the primary conclusion of the report is that the agency should completely dismantle the existing 510(k) program for class II devices and replace that paradigm with a new system explicitly based on safety and effectiveness. Both FDA and industry have signaled their objections to this recommendation and it seems unlikely it will be implemented, at least in the near-term. However, the IOM report does present a few limited but very high-level recommendations that could be adopted within the current framework. It is anticipated that considerable public debate will precede any action on these recommendations, as the agency has announced its intention to collect comments and hold at least one public meeting, before moving forward.

Recommendation to abandon 510(k) process, create new regulatory framework

The IOM Committee on the Public Health Effectiveness of the FDA 510(k) Clearance Process was commissioned by FDA to assess whether the current 510(k) clearance process: (1) optimally protects patients and promotes innovation in support of public health; and (2) if not, to identify what legislative, regulatory, or administrative changes would be recommended to achieve its goals. With regard to these two questions, the IOM Committee concludes in its report that:

  1. The 510(k) process is not intended to evaluate the safety and effectiveness of medical devices, and cannot be changed to specifically evaluate safety or effectiveness, as long as the standard for clearance is substantial equivalence.
  1. It is not possible with currently available information to understand the effect of the 510(k) process on innovation.

Specifically, the Committee questioned the standard of substantial equivalence. Because a determination of substantial equivalence means that the device is as safe and effective as a predicate device, and because devices that were on the market prior to the 1976 Medical Device Amendments (the origin of predicate devices) were not systematically reviewed for safety or effectiveness, the Committee concludes substantial equivalence does not mean a device is safe or effective. At a briefing Friday morning, the Committee acknowledged that there may be some exceptions with regard to certain types of devices for which extensive safety and effectiveness information has been collected over the years.2 However, the Committee's first recommendation is that the agency should abandon the 510(k) process in favor of creation of a new regulatory framework for class II medical devices.

The Committee offered limited guidance as to the desirable attributes of such a new system, specifically that the process should: (1) be based on sound science; (2) be clear, predictable, straightforward, and fair; (3) be self-sustaining and self-improving; (4) facilitate innovation that improves public health by making medical devices available in a timely manner and ensuring their safety and effectiveness throughout their lifecycle; (5) apply relevant and appropriate regulatory authorities and standards throughout the life cycle of devices to ensure safety and effectiveness; and (6) be risk-based. However, concrete suggestions as to the components of such a new system were not presented, and the Committee specifically stated that additional information would need to be gathered in order to design such a framework. One recommendation was that the FDA should investigate whether the de novo down-classification process could be utilized as a model for this new framework, and recommends a pilot program to assess this possibility. However, the Committee recognized that the de novo process in its current form is flawed, and that improvements need to be made before it is used as a model.

In a statement, Jeffrey Shuren, MD, JD, Director of the Center for Devices and Radiological Health (CDRH), while welcoming the IOM report, also made clear the agency does not agree with the suggestion to eliminate the 510(k) program.3 The medical device industry group AdvaMed also issued a statement condemning the IOM recommendation for an entirely new regulatory process.4

Other recommendations that could be implemented within the current framework

Given that both the FDA and industry appear to have rejected the IOM's primary recommendation to create a new regulatory process, it seems unlikely to be implemented. Even in the event that FDA and Congress elected to move forward with the creation of a new framework, this would inevitably be a multi-year process. It is noted that the current 510(k) framework already encompasses (or was designed to encompass) many of the desired attributes of the new regulatory framework proposed by the IOM. Implementing improvements to the current system could certainly meet these six attributes.

Because the IOM Committee does not recommend keeping the 510(k) process in its current form, the report does not generally present detailed suggestions for improving the current 510(k) process. In particular, the Committee stated that it did not have time to fully consider the seven recommendations CDRH had determined would be difficult to implement and therefore referred to the Committee (such as defining "class IIb" devices for which clinical data would generally be necessary). However, the IOM report does present findings and make recommendations that could potentially be implemented without changing the current framework. Many of these relate to potential areas of improvement to the 510(k) process that have been suggested by the agency. If these recommendations, discussed below, were adopted by FDA, they could have an impact on industry in the near-term:

  • Emphasis on postmarket surveillance: Two of the IOM Committee's primary recommendations center on improving medical device postmarket surveillance, including for 510(k)-cleared devices. Specifically, the IOM stated that postmarket data should provide information that can be used in the premarket review period and can be used to inform the development and use of general and special controls. The IOM focused on a "life cycle" approach to regulation of medical devices, as it is recognized that large pre-market clinical studies are not always feasible for devices. The report emphasized that limitations (whether budgetary, legislative, etc.) to the agency's postmarket authority should be identified and removed. One such suggestion is for "conditional clearances" that would implement conditions (for example, collection of registry data) where limited premarket information on a device exists. At the IOM briefing, the Committee expressed disagreement with the FDA's proposal to make premarket requirements more rigorous, and instead favored strengthening postmarket activities.
  • Use of unsafe or ineffective predicates: Within the context of a recommendation that the agency should seek to continually improve its processes and the medical device framework, the IOM cited as an example the agency's inadequate data systems that allow the use of "unsafe" or "ineffective" predicate devices. While not definitively recommending this, the report seems to suggest the agency should have more power to remove devices from the market, as well as prevent such devices from being used as predicates.
  • Additional software validation: The IOM report presents concerns regarding the increasing use of software in medical devices and the potential for "serious software-based device failures." The report recommends that FDA review and update its guidance on software validation.
  • Multiple/split predicates: Although not presented as a finding or recommendation, the IOM report does discuss the controversial topic of multiple or split predicates. The Committee states that "it may be appropriate for multiple and split predicates to play a role in premarket review of Class II devices if the CDRH review team has the necessary expertise to ensure a high-quality review and if appropriate postmarket activities (for example, postmarketing surveillance) are used."
  • Additional findings: The IOM report presents the following important findings or observations regarding the 510(k) process, but does not make specific recommendations for improvements to address these issues:
    • The terms "intended use" and "indications for use" are not well-defined and are therefore susceptible to different interpretations that can cause inconsistency in agency decision-making.
    • The 510(k) process "does not consistently recognize distinctions among devices cleared solely as tools, those cleared for specific clinical applications, and general tools that also have specific clinical applications."
    • The agency is not consistent with regard to the need for clinical data to support 510(k) submissions, the nature of that data, or how the data is used by the agency to make decisions.
    • The de novo process is flawed and has not realized its full potential.

Public debate and discussion

The FDA has opened a public docket for comments on the IOM report and will be accepting comments until 30 September 2011.5 Stakeholders are encouraged to submit comments regarding the IOM's recommendations.

The agency also indicated it will hold a public meeting in the coming weeks to discuss the IOM's recommendations. The meeting date and location have not yet been announced, but should be forthcoming shortly.

Conclusions

It remains to be seen how the agency will utilize the recommendations made in the IOM report. It also remains to be seen how FDA will proceed with respect to the seven specific recommendations for which the agency sought guidance from the IOM Committee, in the absence of such guidance. While it appears unlikely that the 510(k) process will be abandoned in favor of a new regulatory framework, certain of the IOM's recommendations could be implemented as part of the agency's ongoing effort to improve the 510(k) process. However, the IOM recommendations may ultimately have greater impact on the agency's postmarket requirements and policies.

Overall, it can probably be safely said that the IOM report is disappointing to both FDA and industry. The IOM Committee based a good part of its report on the premise that the 510(k) process does not evaluate the safety and efficacy of the device as part of the substantial equivalence review. As anyone who has been involved in the 510(k) clearance process knows, FDA will not find a device to be substantially equivalent if the agency believes it is not safe and effective. The reviewers will simply find a way to not clear a device if there are any serious safety or efficacy issues. This basic false assumption of the Committee is what likely led to the astounding conclusion of the report that the entire 510(k) system should be scrapped. Hopefully, in the next stages of consideration of the report, this basic false assumption can be corrected and the debate can move on to how to optimize a successful paradigm that may need some fine tuning.