The Safety and Performance Based 510(k): A New Pathway for Regulatory Submission

By Nick Schofield, Cognition Corporation

In November 2018, FDA Commissioner Scott Gottlieb and CDRH Director Jeff Shuren publicly discussed the agency’s latest steps in modernizing the 510(k) premarket submission program. In considering the rapid advances in technology and changes in safety and performance criteria, they explained FDA’s new initiative to bring the 510(k) program up to speed. The agency has agency gone a step further since this discussion by publishing a final guidance document that establishes a new pathway: the Safety and Performance Based 510(k).

But what does the safety and performance pathway offer medical device manufacturers, and what does submitting under this new 510(k) look like?

510(k)s, Substantial Equivalence, and FDA’s Least Burdensome Provisions

Before diving into what the Safety and Performance 510(k) can provide to manufacturers, it’s important to understand the precedent behind it. Anyone who’s submitted a 510(k) premarket submission for their medical device understands the role “substantial equivalence” plays in the regulatory review process.

Rather than having to submit new and large quantities of clinical and scientific data to prove your device is safe, there may already exist other devices like yours (known as predicate devices), legally approved and marketed by FDA. As outlined in 21 US Code Section 360(i)(l)(A), proving substantial equivalence for your medical device means demonstrating either:

1. The device has the same technological characteristics as a predicate device, or
2. The device has different technological characteristics, but is at least the same level of safety and effectiveness as a legally marketed device, while not raising different safety and effectiveness concerns from the predicate device.

The substantial equivalence approach defines the 510(k) pathway. As long as manufacturers can provide substantive evidence that the device is at least as safe and effective as those already classified by FDA and legally marketed  — without raising additional concerns due to new technological features or otherwise  — no additional clinical work is necessary.

The 510(k) program exists as a result of FDA’s least burdensome provisions, which also are codified in section 513 of the FD&C Act. Added to the FD&C under both the FDA Modernization Act (FDAMA) and Safety and Innovation Act (FDASIA), the least burdensome provisions govern an approach to premarket evaluation intended to reduce or eliminate burdens on both industry and FDA. This approach dictates that the agency requests only the minimum amount of information necessary in order to appropriately deal with any regulatory concern through “the most efficient manner at the right time.”

Substantial equivalence and the least burdensome provisions coalesce to form the backbone of the 510(k) submission and review process. Both manufacturers and FDA can use these principles to their advantage in premarket activities, including development and submission; however, there is a gap that manufacturers have to deal with.

While FDA employs substantial equivalence and least burdensome provisions in reviewing 510(k) notifications, there are no specific requirements for what either metric actually looks like. Overcoming this gap often is left to manufacturers, but the FDA has taken many steps over the last few years to close that gap, as well. This has led to a number of different methods of premarket notification manufacturers can leverage for submission, including the new Safety and Performance 510(k) pathway.

The Safety and Performance Pathway as an Abbreviated 510(k)

FDA’s endeavors to close the understanding gap related to 510(k)s, substantial equivalence, and least burdensome provisions has led to the creation of three general types of 510(k) submission pathway:  Traditional, Special, and Abbreviated.

Under the New 510(k) Paradigm enacted over 20 years ago, the Special and Abbreviated methods were constructed to further streamline review timelines and processes. The new Safety and Performance 510(k) is categorized as a type of Abbreviated pathway for medical devices:  the pathway envisioned for what FDA defines as “well understood” device types.

Like other Abbreviated 510(k)s, the Safety and Performance path relies on guidance documents, special controls, and recognized standards to analyze conformance assessments and demonstrate substantial equivalence. The Abbreviated submission method differs significantly from the Special and Traditional methods because of its reliance on these three types of established regulatory guidance, standards, and specific controls; Special 510(k)s, for example, focus almost entirely on device modifications and their conformance with design controls, not the device as a whole.

Relying on Performance Criteria

Under the umbrella of the Abbreviated 510(k) program, the Safety and Performance pathway has a very specific and limited scope that aligns with FDA’s substantial equivalence and least burdensome provisions: conformity with performance criteria.

These criteria are formulated as a result of established performance standards identified by FDA. According to 21 CFR 861, performance standards can be established for:

• Class II devices
• Class III devices that have undergone reclassification to Class II
• Class III devices that, as a condition to premarket approval, must reduce or eliminate associated risks

Performance standards can cover everything from performance characteristics and quality processes to testing and labeling. Within this range are safety and performance criteria, which FDA plans to be the sole focus off this new 510(k) pathway. According to the recent guidance, FDA expects submitters under the Safety and Performance method to:

“…use robust versions of those [Abbreviated 510(k)] mechanisms, which contain all the performance characteristics necessary to support a finding of substantial equivalence for a device type, rather than using direct predicate comparison testing to support a finding of substantial equivalence for some of the performance characteristics.”

In other words, FDA wants to see conformance of your device to specific safety and performance criteria as identified in established performance standards. Rather than having to make a direct comparison with a predicate device’s safety and effectiveness data (whether gathered through premarket or postmarket research and surveillance), this pathway is meant for manufacturers to simply show their device performs at the same level of safety and effectiveness as those already cleared and legally marketed.

Eligible Device Types

Because the Safety and Performance 510(k) is very specific in its requirements for submissions, it is limited in scope. As mentioned earlier, FDA insists on only evaluating device types under this program that are well understood by the agency. Currently, there is no published list of device types deemed appropriate for this 510(k) pathway, but FDA expects to publish such a list in the near future. The list will identify performance criteria for each device type, as well as any recommended testing methods, accompanying guidance documents, and other relevant information.

Even without this list available, FDA has criteria for evaluating whether a submitted device is appropriate for the Safety and Performance pathway. Reviewers deem a submission eligible for the program when:

• An eligible predicate device is cited in the submission
• Indication(s) for use/technological characteristics do not raise different safety and effectiveness concerns
• Performance criteria are aligned with one or more legally marketed devices (of the same type)
• The device meets all performance criteria identified by FDA

All of these criteria must be met; if not, submitters still have the option to submit under the Traditional, Special, or Abbreviated pathways.

Benefits of the Safety and Performance 510(k)

This novel method of 510(k) premarket notification has the potential to be valuable for medical device manufacturers. While it relies on substantial equivalence, it does so from a different approach that reduces or eliminates the need for direct comparison, leading to benefits for both the industry and FDA.

1. Optimizing Effort

The Safety and Performance pathway can possibility cut down on the burdens that come with preparing a traditional 510(k). It might seem like an arbitrary difference, but demonstrating that a device performs at least at the same level as a legally marketed predicate can cost less in time and effort than a side by side clinical demonstration. Because FDA understands well the device — its intended use, indications for use, and benefits to the patient population — the philosophy behind least burdensome dictates that additional work to establish that same data in a premarket submission would be unnecessary. Therefore, with an option like the Safety and Performance 510(k), time and resources can be optimized to focus on the critical compliance activities necessary to get the device to market.

2. Streamlined Regulatory Reviews

Because regulators only look at submission data related to conformity with performance criteria, less time can be spent in the review process. Rather than having to focus on whether one device lines up with another perfectly in terms of safety and effectiveness, reviewers only have to establish that the device submission is in compliance with established guidance documents, special controls, and recognized consensus standards. This way, FDA can get more products to market that can positively impact patient outcomes, faster, and without compromising safety and efficacy.

 3. Improved Response Time to Market/Stakeholders

It can take a long time to get a medical device to market, sometimes despite project timelines being met or exceeded. This is a growing issue for users and patients demanding faster response to their needs, especially as technological advancement continues to rapidly accelerate. Manufacturers need greater levels of agility and responsiveness to growing user needs, and expedited regulatory pathways like the Safety and Performance 510(k) can partially provide a solution for that.

Improved response time is particularly powerful for manufacturers releasing new and updated versions of existing products, and/or those looking to expand their product portfolios. Being able to take care of user needs quickly, with a more streamlined pathway, or simply launching a low-cost, well-understood product into the market can have long-term benefits for organizations of all sizes.

Challenges and FDA’s Future Direction

The biggest challenge facing the Safety and Performance 510(k) pathway is its limited scope. Partly, this is a manifestation of its relative immaturity as a premarket notification option for medical device manufacturers, but this issue could persist longer than anticipated. This stifles manufacturers’ abilities to move products to market faster; likewise, regulators are faced with burdens resulting from determinations that submitted devices are not yet supported or recognized by the pathway, even if they know how well the agency understands its device type. For long-term growth and success, both regulators and the industry need to work on managing these challenges now.

Moving forward, it’s reasonable to anticipate the Safety and Performance pathway expanding to become more inclusive and broader in scope. As a function of FDA’s ongoing work to reduce burden and streamline regulatory action, growth of this program is almost an inevitability. Therefore, a wait -and -see approach may better serve medical device manufacturers who are unsure about what the pathway can offer them at this moment; it could provide greater opportunities in the future.

The Safety and Performance 510(k) pathway also is an indication that FDA is working to align its future direction to as nimble an approach as possible. Given the rapid pace of technological change, the rise of mobile medical health, and shifting cultural, economic, and political factors, the agency needs a more flexible and responsive approach to address these concerns. This step may be an early sign of greater regulatory change to come.