The US Food and Drug Administration (FDA) has issued an extensive and long-awaited guidance document on its premarket notification program—also known as the 510(k) pathway—detailing how regulators will evaluate applications in order to determine "substantial equivalence."

Background

The 510(k), or premarket notification, process differs from the premarket approval process in that regulators are partially assessing the safety and efficacy of the device based on its substantial equivalence (SE) to an already-marketed product, known as a predicate device. This allows the company to rely more on the predicate device's record of safety, and less on new clinical evidence.

Accordingly, much of the focus in the 510(k) process is on the ways in which the new device isn't substantially equivalent to predicate devices. As seen in some recent case studies, such as the case of metal-on-metal hip implants, the failure to fully appreciate the differences of new device iterations cleared through the 510(k) process can have disastrous effects on patients.

In 2011, and in the midst of calls for FDA to make changes to the 510(k) process, FDA issued a draft guidance document on the 510(k) program, Evaluating Substantial Equivalence in Premarket Notifications. The intent of the guidance, FDA explained, was "to enhance the predictability, consistency, and transparency of the 510(k) program by describing in greater detail the regulatory framework, policies, and practices underlying FDA's 510(k) review."

The guidance also provided new information about FDA's special 510(k) program, which is used to make modifications to an already-approved device, and its abbreviated 510(k) program, which is used by devices already subject to FDA guidance or standards.

Final Guidance: Focus on Predicates

However, FDA's final guidance of the same name starts off by saying that it plans to address both of those issues separately in as-yet-unnamed guidance documents.

What remains is a fairly straightforward look at the 510(k) process and how regulators plan to approach SE issues in regulatory applications, with a few notable exceptions.

As explained in 2011 by FDA Law Blog, the draft guidance makes several notable changes. For example, FDA said it will no longer accept the concept of a "split predicate," which were used by some companies to compare their product to multiple already-cleared devices.

FDA said that this was "inconsistent with the 510(k) regulatory standard."

However, the agency said it would allow a manufacturer to use multiple predicate devices "to help demonstrate SE in certain circumstances." For example, companies might use multiple predicates "to show that FDA had found similar technology or indications to be substantially equivalent." Even so, companies would rely on "a single predicate" for a finding of SE, FDA said. The rest would simply bolster an application's legitimacy. FDA also refers to this as the "primary predicate" in its guidance.

In other acceptable cases, FDA may accept multiple predicates (e.g. a device with an attached thermometer) so long as neither component affects the function of the other.

FDA also introduces the concept of "Reference devices" in the guidance, explaining that—similar to a predicate device—reference products "may be used to support scientific methodology or standard reference values." The utility of these devices will depend on their similarity to the new device, FDA said.

Because it is not a predicate, FDA's guidance implies that the application of a "reference device" may be most useful in comparing technologies used within devices, instead of the devices as a whole.

In a Federal Register notice, FDA said the final guidance contained few other changes relative to the 2011 draft guidance.

The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)] (FR)