FDA released its highly anticipated proposals for reforming the 510(k) program last week, and industry reps acknowledged that many of the individual recommendations could benefit companies.

But the eventual net impact of a multitude of system changes is difficult to predict, they warned, and anxiety remains high.

The ¹ report, developed by an internal CDRH working group, has been in the works since September 2009. It was unveiled Aug. 4 in conjunctions with a separate ² report with broad recommendations on how the device center could make better use of science in its regulatory decision-making.

CDRH officials say the documents reflect deep thinking about potential lapses in protecting the public and in treating product sponsors fairly.

"Taken together, these preliminary reports show a smarter FDA - an agency that recognizes both sides of our mission to protect and promote public health," CDRH Director Jeffrey Shuren said. "The agency is ready to make necessary improvements to support device innovation while assuring patients receive safe and effective devices."

The 510(k) assessment proposes reasonably substantial changes to the program by which about 90% of medical devices enter the U.S. market, including splitting up the Class II device category into "a" and "b" subsets; reforming the "de novo" classification process for novel, moderate-risk technologies; and solidifying FDA's authority to rescind 510(k)s or determine when products can no longer be used as predicate devices.

Also, in conjunction with the science report, Shuren announced the appointment of Harvard cardiologist and long-time FDA consultant William Maisel as CDRH's deputy director for science, a newly created post.

Splitting Up Class II Devices

FDA acknowledges that 510(k) review times have gone up in recent years, in part because new technologies stress the system and require reviewers to request additional data from manufacturers.

Better defining FDA's evidence requirements could help speed up review times, the 510(k) report suggests.

"In general, most instances where concerns were raised by industry and Center staff about problems with the 510(k) program involved the small subset of devices for which staff requested clinical data," the report notes.

The agency's 510(k) working group recommends splitting up the broad category of moderate-risk devices into Class IIa and Class IIb, where the latter would "typically" require clinical information, manufacturing information and, potentially, post-market mandates.

Class IIb devices may include some implantable, life-sustaining and/or life-supporting devices, such as infusion pumps, that present greater risks than other Class II device types, FDA explained.

The agency may want to require submission of manufacturing information or pre-clearance inspections for Class IIb products, the report says.

FDA should seek greater post-market authorities for these riskier 510(k)s, such as the right to require post-market surveillance studies as a "condition of clearance," similar to post-approval studies for PMA devices, the report recommends.

But the Class II split is not hard and fast, CDRH's Shuren pointed out. "There will always be cases that are kind of in that gray zone," he said.

Evidence requirements would still be determined on a case-by-case basis; for example, some IIa devices may require clinical data, while some IIb devices may not, he said.

Device trade group AdvaMed supports the Class IIb split because it provides "a targeted approach to making changes rather than making sweeping changes to the whole process," Janet Trunzo, executive VP for technology and regulatory affairs, said in an interview.

De Novo Reforms

The 510(k) working group also urges FDA to reform its "de novo" classification process for products that cannot be cleared through the 510(k) process for lack of a predicate, but which do not warrant full PMA review.

"Right now, that process is broken," Shuren acknowledged, echoing a point made by device firms at recent CDRH town hall meetings.

Under the current de novo process, a device must first undergo full 510(k) review and be found not substantially equivalent before it can be considered for de novo review. This "can create a lengthy path to market, making it impractical for many submitters," the 510(k) report notes.

Instead, FDA should consider issuing a not-substantially-equivalent decision quickly and communicate "clearly and early" with the sponsor about what additional information would be needed for de novo review, the report urges.

In addition, the process of issuing special controls guidances - which explain the risks associated with the de novo device and how to mitigate them - may be unnecessarily time-consuming, the report states.

FDA should consider developing a generic set of special controls other than guidance, such as performance standards, post-market surveillance requirements, patient registries and other guidelines, to accompany de novo classification orders, the report states.

Tackling Bad Predicates

The working group also says FDA should take a closer look at predicate devices in 510(k) submissions and consider when certain products should no longer be used as predicates for safety and effectiveness reasons.

FDA should also consider better defining, through regulation, the circumstances under which FDA might rescind a 510(k) or modify the scope of a previous clearance.

Some have questioned whether FDA has the legal authority to rescind a 510(k), but the agency maintains that it has "inherent authority" to reconsider its decisions in certain circumstances, such as when there has been fraud or error, and to rectify its mistakes.

Finally, the working group recommends that FDA disallow use of "split predicates" in 510(k) submissions. This refers to a situation where the sponsor attempts to demonstrate that a device has the same intended use as one predicate and the same technological characteristics as another.

60-Day Comment Period Open

FDA stresses that the recommendations in both reports are preliminary. The agency is accepting comments on the reports through Oct. 4.

At first blush, industry organizations agreed that the changes could be viewed as positives for device makers, but the ultimate impact of the proposals will depend on how they are implemented.

"When you look at the broad-based recommendations, on the surface they all have the potential to be beneficial," Mark Leahey, president and CEO of the Medical Device Manufacturers Association, said in an interview. "But I think it's too early to tell."

AdvaMed's Trunzo added that the long list of specific recommendations may seem fine as standalones, "but if you take them all together, it could change the program significantly," she told "The Gray Sheet" (see sidebar: ³ 'The (New) Anatomy Of A 510(k)').

But others, such as advocacy group Public Citizen, say FDA did not go far enough (see sidebar: ⁴ 'Did FDA Go Too Far Or Not Far Enough?').

After a thorough review of comments, FDA will announce which changes it will implement, "in current or modified form," with projected timelines, Shuren said. "Some of the recommendations could actually be implemented within a matter of weeks or months," he noted.

Recommendations with strong support could be put into effect immediately, while more controversial proposals may be referred to the Institute of Medicine committee that is undertaking a simultaneous review of the 510(k) process to consider in their deliberations, Shuren added.

The IOM 510(k) committee will begin hashing out its recommendations behind closed doors this fall for a final report due next summer (⁵ Also see "Broad 510(k) Reform Still On The Table; IOM Panel Enters Closed-Door Phase" - Medtech Insight, 2 August, 2010.).

- Jessica Bylander ( ⁶ j.bylander@elsevier.com )

FDA Maps Out Potential 510(k) Reforms In Long-Awaited Report

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