I have long been concerned (some might say obsessed) with the distinction between a medical device being “approved” and one being “cleared.” In simple terms, only a Class III device that has successfully traversed the PMA process has been approved. A Class II device that has reached the market via a 510(k) Premarket Notification has been “cleared,” but not approved. Clearance letters used to include the following language: “Also, please note the regulation entitled, ‘Misbranding by reference to premarket notification’ (21CFR807.97).” That regulation says in part that clearance “does not in any way denote official approval of the device. Any representation that creates an impression of official approval of a device because of complying with the premarket notification regulations is misleading and constitutes misbranding.” That is, if it was cleared and you say it is approved, it is misbranded. Most companies are careful about this, but sometimes the press and healthcare providers are not. While clearance letters no longer point to this regulation, the regulation exists nonetheless.
This distinction is more than a mere semantic issue. The difference between approved and cleared is one of the degrees of proof of safety and efficacy that had to be submitted to the FDA, and relates to the degree of scrutiny that the FDA should have applied in reviewing that proof. Generally, Class III devices require a clinical trial as part of their proof while Class II device do not. Understanding this difference should forestall people being “shocked” that some devices, including some that have received a good deal of notoriety, were not tested via a clinical trial before they were marketed.
De novo devices are those for which there is not a substantially equivalent predicate device, and which are therefore not eligible for a standard 510(k) which must compare the candidate device to one or more legally marketed or marketable predicates. However, since some de novo devices might not present the level of risk usually associated with Class III, making them follow the PMA route would be, in principle, unnecessarily burdensome. Thus, a system was created, with direction from Congress, that allows a de novo application that if successful results in a Class II designation and, as a Class II device, a clearance, but not an approval.
However, given my obsession I was disconcerted to find that through the early part of 2014 the FDA listings of de novo devices used the terminology “Approval Letter,” although the letters themselves said nothing about approval. I even had the opportunity to complain directly to the director of the Center for Device and Radiological Health about this seeming anomaly, but he didn’t seem concerned. I only recently discovered that in the later part of 2014, the terminology was changed to “Classification Order” rather than “Approval Letter.” This is what is used today. I confirmed this transition by using the often-fascinating Internet Archive Wayback Machine which collects and saves websites over time (whether the site owner wants them to or not). As part of this exploration, I discovered that my personal website, which I stopped paying for and which no longer exists in the normal way, has been saved by the Wayback Machine 11 times between 2011 and 2016. (This is one of the many ways in which the word “delete” stopped meaning “throw away” and instead has come to mean “put someplace else”, which can include “put someplace else that you can’t readily see but a computer sleuth can find.” A Google search for recovering deleted files provides over 1 million hits.)
Since at the time I missed the 2014 transition from “Approval Letter” to “Clearance Order,” I don’t know if there was any announcement or discussion of this change that I also missed. This leads me to wonder if the FDA is changing things without telling anyone.
William Hyman, ScD, is an adjunct professor of biomedical engineering at The Cooper Union and a consultant in New York. He is also a professor emeritus of biomedical engineering at Texas A&M University.