Newsletter Fall 2018 - Michael Sharp, Ph.D on A Crash Course on 510(k) Clearances


What is a 510(k)?

I still get asked this question 40 years after the Food, Drug and Cosmetic Act (FDCA) implemented the Medical Device Amendment (MDA). Although the answer is more confusing than may be expected, it is important for understanding the regulatory status of medical devices.

As legislators and congressional staff fleshed out the MDA, they recognized – thanks to the efforts of a legion of special interests and lobbyists – that medical devices would need different regulation from that of pharmaceuticals. The diversity of medical devices, ranging from urine specimen collection bottles to intraocular lenses, lasers, MRI imaging, and other high-tech modalities, was a starting place to think about this overall regulatory approach. Using a risk-management approach, the outcome was three risk categories: Class I, Class II, and Class III devices.

Class I devices are low-risk devices. They require general controls, such as Good Manufacturing Practice, to ensure safety. These devices do not require FDA clearance prior to marketing.

Class II devices are higher-risk devices and may be more complex. They require general and special controls to ensure safety and effectiveness. Examples of special controls are mandatory performance standards, patient registries for implantable devices, and post-market surveillance. In addition, Class II devices require FDA clearance prior to marketing, unless specifically exempted. Clearance is obtained by demonstrating substantial equivalence to a predicate device that has been cleared under the 510(k) process. Interestingly, the FDA does not “approve” devices through the 510(k) process, but instead “clears” the product for sale in the US.

Class III devices are defined as those that are life-sustaining, life-supporting, or pose significant potential risks to patients. These devices require general controls, special controls, and pre-market approval. Most cases also require a clinical trial.

Having established the paradigm for risk-based regulation, the FDA created classification panels with experts in a wide variety of devices and  therapeutic areas to evaluate devices for risk assignment. This process established product categories for different devices.

The 510(k) approach

We now have an idea of how the FDA’s process of bringing new devices to market works, but what the 510(k) exactly is remains an open question. In truth, there is no such “thing” as a 510(k). Technically, the term 510(k) describes Section 510(k) of the FDCA: device manufacturers must notify the FDA at least 90 days in advance of their intent to market a medical device, which is called a Premarket Notification. Over time, the regulatory community has adopted “510(k)” as shorthand for the actual citation. Both regulators and sponsors use the term “510(k)” as a noun.

Since the promulgation of the device regulations, these regulations have evolved. Not only do we have the “traditional 510(k),” which is the fallback approach for most devices, but also the abbreviated 510(k). The abbreviated 510(k) is used when the following conditions exist: there are is an FDA guidance for the product type; a special control already has been established; and the FDA has recognized a relevant consensus standard. Additionally, there is the special 510(k), which may be used if a new 510(k) is required for a device modification that does not affect the device’s intended use nor alter its fundamental scientific technology.

Even with this information, there remains confusion about the 510(k). For example, when to use which format? Is there an available predicate device? Can the predicate be convincingly shown to be substantially equivalent to the new device?

When we follow the 510(k) crumbs into the regulatory forest, it turns out to be just as dark and confusing as we fear. But wait, there is a light in the forest! It is not the gingerbread house, but the library of FDA guidance documents. There is a guidance for the contents and format of all the types of 510(k) submissions. There is also a document that helps determine when a new submission is required, as well as another to assist with questions regarding substantial equivalence. There are also copies of 510(k) summaries for previously cleared 510(k)s, which are, of course, not the full submissions, but are nonetheless helpful sources of information. The most helpful document is the Acceptance Checklist for 510(k)s, in which the FDA provides the criteria their reviewers use in determining whether a device will be accepted for filing.

Concern about the 510(k) Process

The 510(k) process has been criticized in the last several years, fueled by recalls and law suits involving cleared devices, such as surgical mesh or metal-on-metal orthopedic prosthesis. As a result, the Institute of Medicine (IOM) reviewed the process in 2011, and the IOM panel found the 510(k) approval process flawed. In their report, the committee noted that the 510(k) approval process “cannot be transformed into a premarket evaluation of safety and effectiveness as long as the standard for clearance is substantial equivalence to any previously cleared device.” The committee was not suggesting, however, that medical devices cleared through the 510(k) process and currently on the market were unsafe or ineffective. In response to these concerns, the FDA issued a “Plan of Action for Implementation of 510(k) and Science Recommendations.”

There are certainly problems with the 510(k), and the FDA has initiated an evaluation of the available options in order to both improve patient safety and maintain an efficient regulatory review process. In any discussion of “510(k) reforms or improvements,” however, one must recognize the difficulty in getting filings accepted. In the data available from the FDA, one third of all submissions are for Class II devices, and only one percent of those are PMA. The remaining two thirds of submissions are Class I devices exempt from review. Any change to the 510(k) process that would increase the need for reviewer resources would make timely clearance difficult and would likely result in longer review times for both Class II and Class III devices.