According to FDA medical device guidance – substantial equivalence in the 510(k) premarket notification process can be clearly determined if you know the underlying legal rules. One of the things I can appreciate about FDA is the clarity of its website and some of its guidance documents.
It wasn’t always this way
My first close encounter of the third kind with FDA was at a conference on integrative medicine sponsored by physician Jim Gordon, Founder and Executive Director of The Center for Mind-Body Medicine. Gordon is a Harvard educated psychiatrist, is a world-renowned expert in using mind-body medicine to heal depression, anxiety, and psychological trauma.
Dr. Gordon had organized a conference on complementary and alternative medical approaches to cancer care.
At the time, there was a strong movement among patients to obtain cancer therapies that had not been FDA-approved.
In my mind, medical paternalism was rampant – the idea that doctor knows best, and that government has the right (and duty) to prevent its citizens from obtaining therapies they choose, in order to protect them from their own ill-advised choices.
In contrast, the ethical value of patient autonomy favors letting patients make informed choices.
Today, we speak about patient empowerment; and FDA has even recently moved to create an advisory commitment on patient engagement.
As Bob Dylan said, the times are a’changing.
Back then, the FDA representative was in a room full of patients, overpowering them with regulatory muscle and insisting that they had no right to choose for themselves.
I was the voice of patient autonomy, patient engagement.
The debate recurred in Hawaii some years later during a conference on integrative medicine sponsored by Harvard and Stanford medical schools. I gave a talk on legal issues in integrative medicine, and an FDA representative spoke on the Agency’s views. One physician stood up and proclaimed that he practiced homeopathy. He asked whether he could get in trouble.
The room was abuzz with concern about liability, investigation, enforcement.
One of the things I said to a reporter around that time was: “the whole (FDA) regulatory structure needs to give more credit to consumers’ ability to make wise choices concerning what goes into their bodies.”
Today I am still passionate about the way the regulatory structure shapes our choices.
I believe that medical paternalism is an antiquated relic of our past, and will be consigned to the ash-heap of history.
Doctors no longer ride on horseback to your log cabin; you summon them on your wristwatch, and soon in your virtual reality headset.
As a practicing healthcare and FDA lawyer, I counsel clients on how to get products to market and stay legally safe, being aggressive in their market while still respecting healthcare compliance and FDA legal guidelines.
This is a dance, and it does require balance. I don’t demonize FDA — although I don’t always agree with the impositions on consumer freedom that I regard as a hallmark of many regulatory decisions. And many regulatory distinctions — such as the line between disease claims and wellness claims – also represents outmoded thinking, in my view.
In some cases, FDA guidance is clear.
When it comes to medical devices, the FDA website and guidance documents leave a good trail of breadcrumbs to follow. What happens from there, is a process. But let’s explore the trail.
The 510(k) Requirement
In a nutshell, you need a 510(k) to market a medical device for which premarket approval (PMA) is not required:
A 510(k) is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective, that is, substantially equivalent, to a legally marketed device…
Once the device is determined to be SE [(substantially equivalent)], it can then be marketed in the U.S. The SE determination is usually made within 90 days and is made based on the information submitted by the submitter.
What is substantial equivalence?
Substantial equivalence means that the new device is at least as safe and effective as the predicate.
A device is substantially equivalent if, in comparison to a predicate it:
has the same intended use as the predicate; and
has the same technological characteristics as the predicate;
has the same intended use as the predicate; and
has different technological characteristics and the information submitted to FDA;
does not raise new questions of safety and effectiveness; and
demonstrates that the device is at least as safe and effective as the legally marketed device.
Substantial equivalence is established with respect to:
- intended use
- energy used or delivered
- chemical composition
- manufacturing process
- and other characteristics, as applicable.
When is a 510(k) required
FDA says that a 510(k) is required when:
- Introducing a medical device into commercial distribution (marketing) for the first time.
- Proposed a different intended use for a medical device already in commercial distribution.
- Modifying a legally marketed device, where the change could significantly alter its safety or effectiveness.
FDA gives guidance on how to find and effectively use predicate devices–the device to which you’ll show that yours is substantially equivalent.
FDA suggests searching the medical device Product Code Classification Database, using:
- names of similar devices – traded name under which the device is marketed;
- manufacturer(s) of the similar device(s);
- marketing status, i.e., preamendments or postamendments device;
- 510(k) numbers for postamendments devices;
- classification information, i.e., product codes, classifying regulations, etc., for your device.
Evaluating Substantial Equivalence in 510(k)s
FDA’s guidance document, The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications (510(k), describes some critical steps in the SE process:
- the appropriate use of multiple predicate devices
- determining whether a new device has a new intended use
- determining whether the different technological characteristics of your device mean you can or cannot use the predicate device
- when FDA will require performance data
- how to develop 510(k) summaries
The good news is that federal law requires FDA to consider the least burdensome means of demonstrating substantial equivalence, when requesting information from the 510(k) submitter.
FDA gives a lot of detail about use of predicates — including multiple predicate devices and “reference” predicates.
The big conundrum: when is the predicate not good enough?
First, some terminology.
The term indication for use means the disease or condition the device will diagnose, treat, prevent, cure, or mitigate, including the patient population for which the medical device is intended. Whereas intended use means the general purpose of the device or its function, and is a criterion for categorizing the product as a medical device.
The big question is, when do the indications for use result in a “new intended use.” Here FDA gives a number of illustrative examples. The focus is on whether a change in the indication for use raises different questions of safety and effectiveness.
For example, a new device used in surgery may raise different risks of infection than the predicate device. FDA may find a new intended use, which means that the 510(k) clearance process is unavailable, and the device maker must go for a PMA, or use the de novo request.
As a second example, suppose a surgical device has been cleared for ablation of cardiac tissue, but now the device maker wants to submit a 510(k) for treatment of atrial fibrillation. FDA will probably conclude that the new device presents questions of safety and efficacy, not demonstrated by the prior device.
A second thorny yet common situation occurs when there is a good predicate with the same intended use, but the technological characteristics differ.
This is where FDA must determine whether the different technological characteristics raise different questions of safety and effectiveness.
For example, a biological indicator uses natural bacterial spores as a biological indicator (through a color change or florescent signal). The new device uses a biological indicator based on recombinant technology / genetic engineering, where the florescent signal indicates something other than bacterial viability — it indicates “plasmid enzyme expression.”
(Now we’re getting into Star Trek sounding language and in addition, hearing about “spores” takes me back to Haley Berry’s battle with psychic ETs in Extant.)
At any rate, it’s pretty obvious even to a layperson that there’s a different technology where the question of safety and effectiveness is not resolved by the prior technology.
Rubber meets road
The guidance document is rich with detail as to the 510(k) process and what FDA might require, when.
Sometimes, technical regulatory consultants can help with parts of the 510(k) submission, especially those that are technical and scientific. But it’s important to get legal counsel at the outset so you know:
- whether you have a medical device
- whether a 510(k) process is possible
- what predicates might exist
- how deeply you’ll have to dip into your angel pocketbooks to get through FDA to market
The rubber meets the road when your investors want to know how you’re positioned on the regulatory path to market. Contact us when you need to navigate FDA territory on your medical device trajectory.
And even if the process seems byzantine, let’s at least give FDA credit for a navigable, information-rich website that helps us figure out where devices stand when they’re in the medical device marketplace.