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FDA's Move to Modernize 510(k) Process Welcomed by Some; Others Stress Caution

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NEW YORK (360Dx) – As the US Food and Drug Administration moves to update the 510(k) clearance pathway for many in vitro diagnostics, some are applauding the step, but others are stressing caution.

Today, the FDA issued a request for comment on plans previously announced in the fall to modernize the 510(k) process used by many IVD manufacturers to bring new lab equipment to market. For some in the lab industry the FDA proposal is a welcome effort to boost controls in an industry where the number of devices on the market can be overwhelming for laboratorians.

"I think it's a step in the right direction. Ten years is going back quite a ways, and when you look at the pace at which new technology is being introduced, it's expanding dramatically," said Mark Birenbaum, administrator for the National Independent Laboratory Association.

Through the 510(k) pathway, manufacturers of in vitro diagnostics and other medical devices obtain FDA clearance by demonstrating substantial equivalence between their product and a device that has already been cleared, known as a predicate device. The FDA is now seeking comment on plans to modernize the predicate approval program by potentially making public the names of devices that are substantially equivalent to older devices, such as devices more than 10 years old. The agency is also weighing other actions, such as potentially sunsetting older predicates in favor or newer ones. The deadline for industry comment on proposed changes is April 22.

Birenbaum is particularly concerned that many in vitro diagnostics cleared through the 510(k) pathway also get CLIA waivers, which exempts them from proficiency testing. (The FDA also released draft guidance aimed at streamlining the dual 510(k) and CLIA waiver application pathway late last year.)

"I think it certainly makes it easier to get waived status, which a lot of manufacturers who produce these types of tests want to get," he said. "There is a lot of oversight that is removed when you get into that waived category and if you have more and more tests waived, pretty soon you have the majority of tests that have very little oversight of how they perform in the field."

The Advanced Medical Device Association, which represents makers of in vitro diagnostics and other medical devices was more guarded in its support of the proposed changes. While acknowledging that regulations must evolve to keep pace with the dynamic nature of technology innovation, the association has some concerns about using a predicate device date as a basis for encouraging modernization.

"This is a complex issue that needs to be carefully and thoughtfully considered to ensure any new policy does not arbitrarily or inadvertently prevent the use of predicates where the clinical and scientific information remains valid," AdvaMed President and CEO Scott Whittaker said in an emailed statement. 

The 510(k) program is the most commonly used device premarket review pathway. In 2017, 3,173 devices were cleared through the 510(k) pathway, representing 82 percent of the total devices cleared or approved, according to the FDA.

However, the FDA separately also announced today a Safety and Performance Based Pathway through which a manufacturer would have the option of demonstrating substantial equivalence to performance criteria, rather than to a predicate device. The FDA plans to periodically review device types and performance criteria for this method to ensure that they are appropriate.

In a statement, the agency said that the Safety and Performance Based Pathway "expands the approach long applied through the abbreviated 510(k) program. Under the proposed program, FDA plans to identify applicable devices and performance criteria through future guidance, "which includes an opportunity for input from stakeholders, and welcomes evidence-based suggestions on what the performance criteria should be for such device types," it said.

Regardless, experts in device approval said that changes to the predicate approval policy may be aimed more at codifying best practices than at changing the way devices obtain 510(k) clearance.

"If I was going to bring a device to market now, theoretically I could choose a predicate that was cleared 25 years ago, but in practice I don't think many companies do that. I think that companies try to choose the most relevant and most recent predicate that's available," said Jon Speer, founder of Greenlight Guru, a quality management software platform designed to help medical device companies bring products to market. "The FDA is trying, at least in my interpretation, to be a little bit more formal about putting provisions in place to ensure that's the case."

In announcing the plan for modernizing the 510(k) predicate approval pathway, FDA officials said the change is specifically aimed at addressing the challenges of evaluating highly complex technology that is rapidly evolving.

"We're considering this approach because the devices we review through the 510(k) program are increasingly complex. They often involve different technological features from the predicates on which they're based," FDA Commissioner Scott Gottlieb and FDA Director to the Center for Devices and Radiological Health Jeff Shuren said in a joint statement.

On the one hand, there are diagnostics and medical devices that were cleared 10 years ago that are still used in clinical practice, according to Shivang Doshi, a director with the consulting firm Boston Healthcare. But the challenge of mapping the new technology risks to older comparable devices might have driven the FDA's modernization decision.

"Probably one of the factors that the FDA had in mind is, should advanced diagnostics really be predicated to older technologies, which inherently might not have the same type of safety and efficacy considerations?" he said.

Gottlieb and Shuren noted that newer devices might be substantially equivalent to older devices but have interconnectivity issues that pose cybersecurity risks that older devices never had to consider. In addition, the 510(k) modernization plan has the potential to not only improve safely, but encourage innovation, they said.

"Sometimes, by relying on old predicates, it can actually make it more difficult for more advanced technology to reach patients since it's harder for an innovative product to bridge to an outdated technology reflected in a decades-old predicate," Gottlieb and Shuren said.

By contrast, a pathway based on more modern predicates could "ensure new products can more easily reflect beneficial new advances," they said.

The 510(k) pathway modernization was one of a flurry of recent announcements aimed as clarifying and streamlining different methods for getting devices cleared or approved. In addition to the 510(k) modernization, and the draft guidance on modified rules for the dual 510(k) clearance and CLlA waiver, the FDA also announced plans for a more efficient de novo pathway for devices for which there is no predicate. Ironically, the FDA announcements have come at a time when device approval regulations in the European Union, which historically were very straightforward, have become more complex, according to Speer of Greenlight Guru. 

"All of it added together seems to be communicating to me, and I think to the industry, that the FDA is very interested in trying to figure out how to get the smoothest, most streamlined, and efficient path to get regulatory market clearance for products," he said.

The FDA's efforts at streamlining are reducing bureaucracy, but not oversight, according to Speer.

"I want to be clear that easier doesn't mean easy," he said. "Regulatory path clarity is important because knowing what needs to be done and when it needs to be done is important, but a 510(k) has requirements that as a medical device company, I am mandated to demonstrate that my product is safe. There is quite a bit of rigor that a medical device has to go through."