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FDA Regulatory Pathways For Medical Devices



How regulatory approval with the FDA proceed when it comes to medical devices? Jeff Smith devotes this whole episode to explain. In a clear and on-point discussion, we get valuable information on the different regulations that cover the different classes of medical devices. Jeff also discusses estimates on how long it takes before a product of a certain class becomes FDA-approved. Most importantly, he explains why investing in pre-market approval (PMA) products makes sense. Stay tuned and learn more!

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FDA Regulatory Pathways For Medical Devices

In this episode, I talk about working with the US regulatory and the Food and Drug Administration. We talked specifically about class 1, 2, and 3 medical devices, and go into how exactly an entrepreneur gets clearance or regulatory approval to commercialize in the United States. Hope you enjoy the episode.

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This episode is all about the FDA. The sequence of talking about US regulatory matters is important when starting a company because it's always a good idea to have the end in mind at the beginning. I'm going to break down the three primary classes of medical devices. Within the FDA, there are obviously food, drug, and medical devices. Many consumer products are regulated through the FDA, but for purpose of this discussion, we'll talk about medical devices.


Class 1 And Class 3 Medical Devices

The medical device classes consist of class one. Think of I'm going to make an orthopedic mallet and I'm going to notify the FDA of my intent to sell. This does not require a clearance or approval from the FDA prior to commercializing. The key distinction with class one is that first, your medical device. The way you intend to market it and to train physicians on how to use this device all conform to the class one qualifications. What makes a product class one? In general, I highly recommend you to go to the FDA's website FDA.gov. There are excellent guidance documents on what a class one medical device is.


For purposes of this discussion, think of a class one device as a general use instrument. Because it is a general use, the FDA cleared or approved labeling for exactly what industry can do to promote it. It's very broad. The watch out here is when you take a class one instrument. Going back to the orthopedic mallet, if you register with the Food and Drug Administration, first, you have to register your establishment. That's the name of your company. Next, if you register the specific product in this case, the orthopedic mallet, you have to maintain a quality management system, which we'll talk about in another episode, but you've effectively registered with the FDA.


It's important to know that you can't say this product is FDA approved. You can't make a claim that when you use your therapeutic mallet in a specific way, you get a specific clinical outcome or even an economic outcome. You cannot make claims about this product because it is being regulated, which means your ability to promote and market the device is very limited and it's restricted under this general use. If you were to take your orthopedic mallet, registered with the FDA as a class one instrument, surgeons could begin using it.

UMN 20 | Medical Devices
Medical Devices: Class 3 has the highest regulatory bar. This is traditionally reserved for when pre-market approval (PMA) is required.

You could promote it for the use of malleting something like an orthopedic mallet would be used. If you turned it into the magic mallet procedure that required some kind of enabling technology and imaging modality, that is an example of taking a general use instrument and then promoting it for a very specific technique. It gets even more off-label if you're using that specific technique to provide clinical benefit for a very specific patient population. In summary, class one is generic general use.


We're going to skip class 2 and we'll go right to class 3. Class three has the highest regulatory bar. This is traditionally reserved for Pre-Market Approval is required, otherwise known as a PMA. The whole basis for a class three medical implant or device is that it's certainly not general use. That's why I started with class one. It's not class one. This is an implant. It's going to go into the body and do some very specific things.


The fact that it's being implanted creates a level of risk. It's a safety and efficacy risk. Because this is a medical implant and we're exploring class three, the whole idea behind it is that there's nothing else like it. We'll come back to that when we discuss class two. For purposes of the class three description, a class three medical device requiring a Pre-Market Approval has the highest level of novelty. You've basically invented something that the FDA has never regulated, or if they have, let's say it's the 7th or 8th cervical disc arthroplasty device, there's already been a well-established path to regulate this type of implant. It's like a class effect that you would see in the pharmaceutical industry.


FDA has determined this particular product will be regulated through the class three pathway. That means the sponsor of this implant is going to submit a Pre-Market Approval or PMA. There's a great guidance document on preparing a PMA submission. The general idea is class three PMA products almost always require clinical evidence. Because it is a product that's not currently on the US market, in order to do a clinical trial is evaluating the safety, efficacy, and other endpoints of a PMA product, it requires the sponsor or the company that's developing this product to file for an Investigational Device Exemption.


Exemption being the keyword there. What is being exempt is after much discussion on the clinical trial design on the potential safety relative to the potential risk, the FDA is saying, “This product that the company is seeking to produce meets the standards of an IDE and the protocol and the way the study sponsors are going to evaluate the clinical outcomes of this product. We are willing to give you an exemption and you can do this clinical trial here in the United States as long as each of the sites where you attempt to enroll patients have independent Investigational Review Board approval or IRB approval. In some countries, it's called an Ethics Committee.”


Regulatory matters are important when starting a company, because it's always a good idea to have the end in mind at the beginning.

This is where the hospital and the study site’s own local bodies have determined the potential risk to the patient. That's being offered a clinical trial, in this case, Investigational Device Exemption or IDE study, the potential benefits outweigh the risks. This is generally an ethical application of using human subjects for clinical trials.


What happens for the PMA submission in class three medical device is it takes significantly longer because it means first, the company usually has to do some early performance evaluation, whether it be on a biomechanical model, bend testing using mechanical rigs, or possibly depending on local jurisdictions, international clinical evidence collected, and always complying with the local regulators of that country.


When the sponsor of a PMA submission has sufficient performance data, they can then begin to engage with the FDA through the form of A Q-Submission or often referred to as the Q-Sub now takes the place of what was known as the pre-IDE meeting. I highly recommend the Q-Submission because what it does is it gives you an opportunity to meet whether face-to-face or virtually the FDA branch that's going to be regulating your device. This is your opportunity to, first of all, let them know your passion for this problem, and this unmet need that you believe needs to be served. Bring it to life what these patients go through.


You can methodically layout the very systematic approach you've taken to understanding risk, failure modes, and display the performance evidence that you've collected on your product. If this meeting goes well and it will be a collaboration, the FDA will give you a sense of the form of call notes. It's important for the sponsor to take the meeting minutes of this discussion and then circulate them to FDA so that they can agree that your summary of the points and the FDA's feedback are in full alignment. It is with the Q-Submission meeting notes and the discussion from that meeting that will allow you to prepare an IDE submission.


The IDE submission is a fully prepared clinical trial incorporating FDA's feedback from the Q-Sub meeting. When the FDA says, “This clinical trial is now approved,” you've created value for your business. It's an important milestone for a class three company and product being developed by a company because it shows a path to complete clinical data collection that FDA has said, “Should you meet a particular endpoint, whether it be non-inferiority to other implants in a similar space, or in some cases, even a superiority bar?”

UMN 20 | Medical Devices
Medical Devices: Class 3 medical devices, almost by definition, have clinical evidence of specific marketing claims.

You will know what exactly has to happen next. To finance the clinical trial, investors will understand the relative costs and timeline. That will help to give a sense of what they're willing to invest and at what valuation. A pre-IDE or a Q-Submission followed by an IDE submission, followed by an IDE-approved clinical trial is a big milestone for our business. That's now a class three. We've covered class one, generic general use and limited ability to promote specific applications. Let's talk about class two.


Class 2 Medical Devices

Class two is the most common regulatory pathway by FDA for medical devices because what they attempt to do is calls out. It appeared in time in the late ‘70s when many medical devices were regulated. FDA says, “Here's what we're going to do. There are so many categories within surgery and med tech. We're going to classify these products into specific codes. Our belief is that in aggregate, they represent the majority of medical implant instrument types. Moving forward, they will now serve as product kits. When industry or academia develop a new medical device, we will determine their regulatory status based on the existence or nonexistence of a predicate.”


Being able to understand how to review CDRH, which is the medical device branch of the FDA, and seek out creative predicates that could serve as a valid predicate for your novel medical device. Yet there's sufficient leeway within that category where there are enough different design features within the predicate class. Some of the novel features of your implant could still meet and valid predicate for a class two submission.


We'll take something generic, which is an orthopedic screw. There are orthopedic screws cleared by the FDA through the class two pathway, and now a company wants to develop an orthopedic screw. The first thing the company does is look at the 510(k) database. The database will have product codes. For instance, the orthopedic bone screw is UWC. You look at the definition of that product and you want to make sure that what you intend to develop could reasonably fit that and pay specific attention to all the language used because if your implant meets this definition, some major features are different.


Let's say, it goes to a different body. It has some new features. It's powered or as a material, that's never been evaluating the body. That's not going to be a predicate, but what if the sponsor of the submission for a class two clearance, which is called a 510(k) submission, is very well described as what the submitting company has to substantiate.


FDA labeling is such an important concept because it really gets to the core of what FDA ultimately grants a new medical device – marketing clearance.

The first one is, does a valid predicate exists? There's a 510(k) Decision Making Flow Char on the FDA website, “Is there a valid predicate?” If yes, does this product have any design features that represent new types of safety and efficacy questions? For instance, if you're going to do an orthopedic screw that has some magnetic feature that makes it change its shape or a design change in a typical screw, is that going to raise new types of safety and FC questions?” If the answer is no, then you can continue down the flow chart.


Are there performance data that exists that can prove substantial performance equivalent to the predicate? In the case of orthopedic implants, that typically comes in the form of bend testing. I say bend because it means you're in a mechanical engineering environment where you're designing setups and these rigs allow you to do things like apply an axial load and dynamic compression over a series of time. What's nice about bend testing is there is a body called the ASTM, which publishes recognized standards for evaluating certain features of not just medical implants but for our purposes for medical implants. For screws, there's a very specific standard on how much load a screw implanted into bone needs to withstand.


If you've met the requirement that there is a valid predicate, that does in fact exist is step one. Step two, does your device have any unique design characteristics that could? I use could because that's an important word. That is where FDA has some leeway. It's their subjective opinion. Could it represent new types of safety and efficacy questions? If not, are there recognized standards and performance data that helped prove substantial equivalence to the product yet?


That's an important feature because, for all the predicates out there, there are multiple, in some cases, hundreds of 510(k) class two cleared products in that predicate category where FDA has all their performance data. As the submitting company of a new 510(k) submission, you don't always have the benefit of knowing what that performance data is or the results but there are ways to triangulate. Specifically, there are some great testing labs that do this bend testing.


They're certainly not going to break confidentiality, but what they can do is tell you a range that they see. If you met all that criteria, you prepare your 510(k) submission, which is very much feature the flow chart concept of, “Is there a valid predicate? If so, what is it?” It's then the design characteristics of your implant and why they conform to this predicate concept. You then have to determine what is your intended FDA labeling.

UMN 20 | Medical Devices
Medical Devices: Clinical evidence is the currency of the realm.

FDA labeling is such an important concept because what it says is it gets to the core of what the FDA ultimately grants a new medical device, which is marketing clearance. It gives the industry sponsors the ability to promote and market a medical device for a specific purpose. It's important to know exactly what is your intended FDA-cleared labeling. When all that is prepared, the FDA submission is submitted. One of the features of a 510(k) which is desirable is that the FDA has a statutory timeline where they have to review and make a decision within the span of 90 days.


That 90-day is FDA's time with the document. In the event that they need additional information, they would typically send it to the sponsor in the form of a letter. It's usually very well detailed. When they do that and ask questions, they stop the clock. It's a nice way of looking at it. If you have a thorough FDA submission and you've prepared all data in the guidance document for submitting 510(k)s, I always like to think it could take six months. When you send it to the FDA, there's a process by which they approve that the submission is indeed in order. All the specific sections are called out again in the 510(k) guidance document or are a review that the predicate does in fact exist.


There's even a quick review of whether or not that predicate is valid. At that point, once your submission is accepted, it's usually within 45 to 60 days that FDA will respond to the 510(k) submitting party and say, “We've received it. We have the following questions. Please respond,” clock stopped. You have time to respond to their questions because sometimes you might need to do more work, maybe repeat a bend test.


You also have the ability to request a 180-day extension, which gives you another six months. In the event that the FDA requires you to provide some type of evidence or data that's going to take you longer than six months, you can withdraw that 510(k), and that stops your clock, then you can take as long as you need.


Why Pursuing PMA Products Makes Sense

The last point I would mention on these class 1, 2, and 3 regulatory pathways for getting marketing clearance through the FDA for a medical device is number one, class three medical devices almost by definition have clinical evidence and specific marketing claims. These are incredibly valuable when a company or an acquirer of a certain technology attempts to commercialize it because clinical evidence is the currency of the realm, as they say. What I mean by that is in order to get surgeons to take your product seriously, physicians, or health care providers, they're scientific-minded people that make scientific decisions based on evidence. Having that, when going to a new potential customer is incredibly important.


It is a better proposition to pursue PMA products. Although they take longer to commercialize, the path is all about clinical evidence and the underlying value of the asset you're working so hard to develop is always going to be a function of the evidence that you generate.

To say it another way, it's hard to do without it. The second thing is, should you uncover a need for your target customer and that customer decides to want to use your product? If it's going to be implanted or used at a hospital, hospital facilities want to know that you have clinical evidence before they approve your product to be bought at all. Clinical evidence, although it takes a long time, accelerates greatly the commercial ramp of a medical device.


It is also, for the potential investor and acquirer of this technology, substantiates the value, the IP, and everything that your company is trying to do so. It de-risks the next financing and phase of the company's development. There was a time when people thought 510(k) products were somehow superior because you could commercialize quickly, get some meaningful amount of traction, and get revenue. On the basis of regulatory clearance, an early commercial traction company gets acquired.


You can do that all in a relatively short amount of time. In the last years, the time from founding a company to exiting a 510(k) product is now longer than ten years. I saw a report, it's approaching eleven years in the average time from founding to exit for a 510(k). The class three or PMA product is closer to 8 to 9 years. What that tells me as someone that likes to start medical device companies, I believe it is a lower risk proposition for the entrepreneur, investors, and ultimately the patients and users to pursue 510(k).


It is a better proposition to pursue PMA products because, although they take longer to commercialize, the path to commercialization is all about clinical evidence. The underlying value of the asset you're working so hard to develop is always going to be a function of the evidence that you generate. I hope you enjoy the episode. Stay tuned for more.

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Thanks for reading this episode. Hopefully, you found the description of class 1, 2, and 3 medical devices helpful. If you have any questions, feel free to contact me on LinkedIn or hit me up at Jeff@JeffSmith.com. You can always find my content at www.JeffSmith.co.


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