The system by which most medical devices reach the market, known as the premarket notification or 510(k) process, has been subject to a considerable amount of criticism in recent years, with detractors claiming that it is both too rigorous and not rigorous enough, and legislators ordering the US Food and Drug Administration (FDA) to scrap planned changes to the process in favor of one yet to be built.

Now the influential trade industry group AdvaMed, the largest medical device industry group in the US, is out with a wishlist of sorts that argues that while the overall system remains sound, it could stand some improvements.

Background

The 510(k) program is built on the premise that, in general, if a device has already been approved by FDA, a device that is "substantially equivalent" to the predicate device should, in theory, be safe for use as well. The devices that are cleared through the 510(k) process are still rigorously tested, but generally avoid the costly clinical trials that can be a burden on companies' bottom lines, as well as the substantial premarket application (PMA) fee of $248,000. In comparison, a 510(k) costs less than $5,000 to file.

The program has also been wildly successful in some respects, with approximately 98% of all devices reaching the market via the 510(k) pathway.

But that doesn't mean the program is without its flaws. It has come under fire during several incidents in recent years involving devices that relied on either unsafe predicates, or deviated sufficiently enough from the predicate devices as to render them unsafe for human use. The most prominent example of all may well be Johnson & Johnson subsidiary DePuy's metal-on-metal hip implants, which relied on several changes, known as a "split predicate" device. Those changes, however, resulted in several unexpected mechanical failures, injuring patients and requiring numerous surgical revisions. In light of those problems, FDA has since required the devices to be approved under a PMA as a Class III (high-risk) medical device.

At times it has also come under fire from members of industry, some of whom have alleged that the program has grown increasingly onerous over the years, delaying market entry for otherwise safe devices, especially in relation to the expeditious approval system favored by EU member states.

AdvaMed: 510(k) is OK

The program, in other words, may be widely used, but it is not widely loved. Which makes a new white paper just published by AdvaMed a bit surprising: It's generally supportive of the system as a whole even as it recommends that a few changes be made to shore up some perceived shortcomings.

"The agency's current guidance on 510(k) modifications has a more than 15-year track record of providing clear direction for companies and FDA reviewers on when a change warrants a new 510(k)," wrote Janet Trunzo, senior executive vice president for technology and regulatory affairs at AdvaMed, in a statement.  The current process is one characterized by strength, she added, noting that it "affords American patients timely access to new medical technology innovations."

Still, AdvaMed's comments, which were made in advance of a meeting on the 510(k) process, come after legislators demanded that FDA drop a proposed revision to the 510(k) guidance and restart its proposed revisions and revert to its 1997 standard. In other words, AdvaMed does like the 510(k) process, but only after legislators succeeded in removing the major changes it didn't like about the process.

A Path Forward?

This unique situation leaves regulators and industry both with a clean slate from which to build a new and improved system - an opportunity that AdvaMed seems to be taking advantage of in order to argue for changes it favors.

"Although we make specific recommendations on how that [1997] guidance [on 510(k)s] can be further strengthened, we continue to believe that it provides the necessary direction and flexibility to ensure that modifications are adequately assessed, and when appropriate, submitted to the Agency," AdvaMed writes in its white paper.

Even more to the point is a sub-heading later on in the white paper: "It is unclear that there is a real problem that needs to be solved," referring to FDA's attempts to make changes to the system to require more change notifications. The organization noted that the 510(k) process is used by tens of thousands of medical devices constituting hundreds of thousands of 510(k) submissions since the formation of the system. A few bad apples aside, it says, the system has worked remarkably well for one that was never explicitly laid out as such.

Proposed Recommendations

But if the system is doing alright, according to AdvaMed, what improvements might be made to address some of its deficiencies? It lays out three tenets it says should form the foundation of any system going forward:

1. Only those changes that could significantly affect safety and effectiveness should require a new premarket notification
2. The determination of "could significantly affect safety and effectiveness" should continue to be made through substantial reliance on the Quality Systems regulation.
3. A change that "could significantly affect the safety or effectiveness of the device" is a change specific to an individual device that has reached a threshold, as assessed by the manufacturer in accordance with established procedures, when determined by the results of design verification or validation procedures in compliance with the requirements of the Quality System.

From there, the organization says three specific changes can be made to bring the 1997 510(k) guidance up to speed:

1. An explicit requirement in the guidance document that when a change is made to a specification, method, or procedure, each manufacturer should evaluate the change in accordance with an established procedure to determine if the submission of a premarket notification is required, and to require the retention of records of this evaluation and its results.
2. An explicit requirement in the guidance document for each manufacturer to establish a procedure within its quality system to ensure that after the design requirements are established and approved, changes to the design, both pre- production and post-production are also reviewed, validated (or verified where appropriate), and approved.
3. Explicit statements at every stage of the guidance document that the responses to each question in the decision trees must be made based on the results of validation testing (or verification testing, where applicable) undertaken in compliance with the requirements of 21 CFR 820. This would provide assurance to the Agency that the questions in the 1997 guidance document are not being arbitrarily answered; rather, that they are being addressed through an FDA-sanctioned process and documented accordingly.

What remains to be seen, then, is whether FDA shares AdvaMed's vision for an overhauled 510(k) system, or instead wishes to keep elements of its now-withdrawn guidance in place going forward. What is clear, however, is that this time around industry is in a much stronger bargaining position now that legislators - many of whom were skeptical about the performance of FDA's device regulatory unit during 2012 negotiations over the FDA Safety and Innovation Act - are keeping a close eye on the new 510(k) proposal.

A report is due to Congress within 18 months of the passage of FDASIA, giving FDA approximately 9 more months in which to revamp the system.

AdvaMed's Whitepaper on the 510(k) Process