In this episode of the Global Medical Device Podcast, Etienne Nichols sits down with regulatory expert Dr. Mike Drues to demystify the pre-market approval (PMA) process for medical devices.

They delve into the key differences between PMAs, 510(k)s, and de novos, bust common myths, and explore strategic advantages for companies willing to pursue the rigorous PMA pathway.

Mike explains the nuances of the “six-year rule,” alternatives like the humanitarian device exemption (HDE), and the evolving role of clinical data.

With insights on using PMAs as a competitive strategy and overcoming internal resistance to high-risk device development, this discussion is essential for MedTech innovators looking to turn regulatory challenges into opportunities.

Key Timestamps:

• 00:00 – Intro and Greenlight Guru's Quality Management System software sponsor message
• 03:15 – Introduction to Dr. Mike Drues and his background in PMAs
• 05:45 – Overview of PMAs and when they should be used
• 11:30 – Are PMAs the only pathway for Class 3 devices?
• 16:20 – Types of PMAs: Traditional, Modular, and Streamlined
• 22:40 – Advantages of PMAs compared to 510(k)s and de novos
• 27:50 – The strategic use of predicates in the PMA process
• 33:00 – Clinical data requirements and misconceptions for PMAs
• 41:10 – Post-market requirements and differences for PMA devices
• 47:25 – Innovation and the future of PMAs: Six-year rule and potential EU approvals
• 54:30 – Final thoughts on overcoming industry resistance to PMAs

Standout Quotes:

1. "Don't be afraid of the big bad PMA—often, the regulatory burden is justified for complex devices tackling high-risk conditions." – Dr. Mike Drues
2. "Regulatory professionals know the rules; the best ones know the exceptions. When it comes to PMAs, there are more options than many realize." – Dr. Mike Drues

3 Key Takeaways:

1. PMA Isn’t the Only Path for Class 3 Devices: Companies can consider alternatives like the Humanitarian Device Exemption (HDE) and Product Development Protocol (PDP) to reduce the regulatory burden.
2. Strategic Use of PMAs Can Provide a Competitive Edge: By choosing the PMA route, companies can create barriers for competitors, potentially driving smaller rivals out of the market.
3. Clinical Data Isn’t Always Mandatory for PMAs: While most PMAs involve clinical trials, there is flexibility in requirements, offering an opportunity to minimize the scope and cost of clinical studies.

References:

• Previous Greenlight Guru Webinars by Dr. Mike Drues
• Greenlight Guru’s QMS Software
• Etienne Nichols’ LinkedIn

MedTech 101:

PMA Pathway Explained – Pre-market approval (PMA) is the FDA's strictest regulatory pathway, typically reserved for Class 3 medical devices with higher risks. Unlike the 510(k) pathway, PMA requires evidence of safety and efficacy, often through clinical trials, but the scope can vary. There are traditional, modular, and streamlined PMA types, each with unique requirements.

Audience Engagement:

Poll Question: "Have you considered using a PMA as a strategic advantage for your MedTech device? What challenges do you anticipate?"

Feedback:

We’d love to hear from you! Share your thoughts on this episode, or suggest topics you’d like covered. Email us at podcast@greenlight.guru and don’t forget to leave a review to help others find us.

Mike Drues: Welcome to the Global Medical Device Podcast where today's brightest minds in the medical device industry go to get their most useful and actionable insider knowledge direct from some of the world's leading medical device experts and companies.

Etienne Nichols: Do you want to streamline your quality management processes and focus on what really matters developing life changing medical devices? Greenlight Guru's all in One Quality Management System software is designed for medtech companies, helping you manage design controls, risk management, CAPA and more, all while staying compliant with FDA and ISO standards. Say goodbye to fragmented systems and hello to simplicity. Join thousands of medical device professionals using Greenlight guru. Check out wwgreenlight.guru today to learn more.

Etienne Nichols: Hey everybody, welcome back to the Global Medical Device Podcast. My name is Etienne. I am the host for today's episode. With us today is Dr. Mike Drews, a familiar voice on the podcast and we have. I don't know how many podcasts you've done with us Mike. We'll have to go back and get a count. Maybe we could do the best of Mike Drews through the years with Greenlight Grid at some point, but how are you doing today?

Mike Drues: I'm well, thank you Edien, and as always, I appreciate the opportunity to have this discussion with you and our audience today. In terms of your question, I think that it's now approaching about 150 podcasts in total and I don't know how many webinars. So I've been fortunate to be working with Greenlight for many, many years.

Etienne Nichols: Awesome. Well, we appreciate it and we hope to continue the partnership as well. So today I want to talk about Pre market approval PMAs and so maybe to introduce this topic, Mike, would you want to talk about what is a pre market approval or PMA and when should one be used?

Mike Drues: Yeah, great question Eddie. And unfortunately a lot of people are scared of the big bad PMA because for the reasons that we'll talk about today. But I think that's very unfortunate because although the regulatory burden of a PMA overall is greater than a 510k or de novo, it is justified because keep in mind, Edien, that usually the technologies that go into PMA devices are more complex in a biomedical engineering sense than a 510k or a DE novo device. Usually the indications or specifically the pathophysiologies that the device is intended to address are more complicated and usually the risks are higher. So although it is more time consuming and expensive as a general rule to bring a PMA device onto the market, there are reasons for that and the reason why I bring that up in part, edien, is because I work with a few companies, including a couple of very, very large medical device companies, who, as a matter of company policy, if have a device that even might be a Class 3PMA, they will not pursue it, they will not develop it. And I think that's just very unfortunate in terms of how the PMA compares to the rest of the medical device universe. The PMA is the second most commonly used pathway to market. Second, obviously to the 510, roughly about 5% to maybe as much as 10% of devices that come onto the market come onto the market as a, as a pma. However, the other interesting statistic that I think it's important for our audience to understand is about 70 to 90% of PMAs that are submitted to the FDA, about 70 to 90% of them are rejected first time out of the box. They result in what's called a major deficiency letter. And as we've talked about before, I think it's unfortunate that we as an industry have devolved, not even evolved, but devolved to treat the FDA as our, essentially our elementary school teacher. Here's my homework assignment. Will you please mark it up and give it back to me? This happens in the 510 world, this happens in the de novo world, and this also happens in the PMA world. So finally, the direct answer to Your question is PMAs are usually used for Class 3 devices. But please notice I'm parsing my words carefully. I'm saying usually use average regulatory professionals know the rules, the best ones, know the exceptions. There are a few, not many, but a few Class 3 devices, mostly in orthopedics and a few in Cardiology. They're Class 3 devices, but they are 5.10K. And let me say that one more time. There are a few devices in orthopedics and also in cardiology that, that they are class 3, but they are not. They don't require a PMA. They require a 510k. For reasons I won't get into here, but this is an example of, you know, when I used to teach medical school, I would say to my med students, when you hear hoofbeats, think horses, not zebras. So the class 3 devices that I'm referring to that are 510k able, those are the zebras, not the horses.

Etienne Nichols: I want to just clarify one of the things that you said. So you said the PMA is for class 3. Makes sense what you were saying about those class 3 devices that use the 510k but all PMAs are class 3? Is that accurate?

Mike Drues: That's an interesting question. As far as I know, I gave you the other exception, that some class 3 devices are 510ks. Kudos to you. Adion. Because that's a question that you stumped me on. My guess is there aren't any non class 3 devices that are PMAs. But I could be wrong. I'll have to. I'll have to look into that. I don't think there are, but there might be.

Etienne Nichols: It doesn't make sense that they would be immediately.

Mike Drues: But yeah, yeah, I mean, every rule has an exception and every exception has an exception, and so on. But that's. That's a situation that I did not consider.

Etienne Nichols: Well, let's go to another question that I'm sure you'll have answers for a lot of questions that really are more pertinent to the audience. So one of the questions is, is PMA the only option for a Class 3 device?

Mike Drues: Yeah, great question, Eddie. And the short answer is, absolutely not. Absolutely not. Another reason why so many companies are so hesitant to pursue a Class 3 device is because they think that if it's Class 3, the PMA is the only option. And that is, in fact, not the case. It's certainly the most common option, but it's not the only one. Additional options that we have in the Class 3 universe would be the Humanitarian Device Exemption or the HDE, as well as the Product Development Protocol, the PDP. Now, for those that are interested, I did a webinar for Greenlight, I think, a couple of years ago on medical device pathways to market, where I go through a description of all of the different pathways and examples of each. So if you're not real familiar with the HDE or the pdp, I would suggest, you know, maybe watching that webinar, we can put a link to that on the. On the site for this podcast if you want. But in general, an hde, a humanitarian device exemption, is kind of the medical device equivalent of the orphan drug program. In other words, there are limitations as to the number of devices that you can sell per year. It's currently 8,000 or less, and the amount of money that you can make. However, here's the big advantage of the HDE for most medical devices. We're required to show that the device is safe and effective. But please notice I'm parsing my words carefully. I'm saying most, I'm not saying all the HDE is an exception. The HDE has no efficacy requirement. Instead, what the regulation, what the requirement is, is we have to show what's called probable benefit. Probable benefit. Now, I don't have time to get into details of exactly what probable benefit means, but in a nutshell it means efficacy but at a much lower statistical power. In other words, efficacy with far fewer patients. And so in the Class 3 universe, if I can, I love to bring devices onto the market first as an HDE because it's easier and usually faster, and so on and so on, and then go back to the FDA later as a label expansion and do it as a PMA for a bigger market. And I've done that successfully many times. The other pathway that I mentioned is the product Product Development protocol or pdp. It's an extraordinarily uncommon pathway to market, but the way I like to describe it, it's sort of a self directed pma. In other words, you agree in advance with the FDA as to what you're going to do and then once you finish doing what you're going to do, then FDA approves it as a pma. So there are some advantages in certain situations, especially if it's well established technology. So bottom line, you can combine these pathways in many, many different ways. For example, you don't, you know, I've got devices on the market that if a device is used in one part of the body, it's a pma. If the same device is used in another part of the body, it's a 510k. So there's a lot of ways that we can combine these things. And if you want to take it even one step further, edien when it comes to combination products, when you start combining, you know, the PMA pathway with, with the NDA for drugs or BLA for biologics and so on and so on, there are a lot of different possible combinations. So again, I would refer to our audience to do some of my previous green light webinars that the. Well, I did a PMA webinar, I did a classification webinar and so on.

Etienne Nichols: I'm taking some notes here to put those in the show notes.

Etienne Nichols: So those of you who are listening.

Etienne Nichols: Feel free to check that out after the show and we can, you should be able to find those as well. So. So you mentioned a lot of different pathways or different options and different ways of doing things. And I love that you, especially the HDE to pma. We may have to go back to that a little bit later when we get to clinical evidence. But I did have a question about PMAs and are all PMAs the same? Are all PMAs created equal.

Mike Drues: Yeah. Again, Elian, great question. Short answer is no. There are, pardon me, there are various subtypes of PMAs, just like there are various subtypes of 510 traditional, special, abbreviated. Now, the SP, the safety and performance base. There are three different subtypes of PMAs. The traditional, the modular, and the streamlined. Again, I don't want to get into the details of all three of them, but for right now, let me just say that although the traditional is the most commonly used, just like the traditional 510k is the most commonly used, the modular PMA in many situations is my personal favorite, especially when you have very, very complex devices, say like a left ventricular assist device that has lots of different mechanical components, electrical components, software components, and you're talking about years of development to get that onto the market. The problem of doing a traditional PMA is you have to wait until you have everything and submit it to the FDA all at once. And then FDA might come back and say, well, we have a problem with what you did five years ago.

Etienne Nichols: Yeah.

Mike Drues: So the modular PMA basically allows you to create sort of modules, a preclinical module, a clinical module, and so on. And when you complete each module, you can submit that, say your preclinical module. And while FDA is chewing on your preclinical module, you're now working on your clinical module. So I love the modular pma. A lot of people are not aware of it, especially for long or complex devices. If you have a simpler pma, then it might not be necessary.

Etienne Nichols: That makes sense. So when we talk about these, the PMA, these different types of PMAs, I mean, that's interesting and I think like you said, it gets pretty nuanced. But I'm curious how to how the PMA differs from other pathways. So the PMA as it differs from that 510k, and especially as it differs from the de novo.

Mike Drues: Yeah, great question. And so the most obvious question most of the time is that PMAs are for Class 3 devices, whereas 510Ks and De Novos are for Class 2 or lower devices. That's obviously the biggest difference or one of the biggest differences. But as a general rule, usually PMAs require more time and money. But again, as I said before, that's justified because you're talking about more complex technologies, more complicated pathophysiologies, higher risks, and so on. Pardon me. And as a result, the regulatory burden of PMAs as a general rule is higher than 510s and de novos. Unfortunately, when it comes to user Fees. The user fees for PMAs are higher than they are for 510s and even DE novos, to be fair. Obviously, obviously, a PMA requires more resources, more effort for FDA to review and therefore it's going to, you know, be a little more costly. But on the upside, your first PMA is free.

Etienne Nichols: I didn't know that.

Mike Drues: There you go. It's an encouragement that, you know, to try to get companies to work in the PMA universe, especially small and startup companies, because as you can appreciate, Eddie, and that's not an easy thing for any company to do, but especially a small company or a startup. So by saying that you don't have to pay a user fee for your first pma, that could be an advantage. And then one other advantage of going the PMA route is that usually your reimbursement is higher. So in other words, as a general rule, the higher the class, the higher the reimbursement. So everything else being equal, a Class 3 device is going to be reimbursed at a higher level than a Class 2 device, whether it's a 510K or a DE novo. So although in the short term it might cost you more money to bring it onto the market, in the longer term, you actually might make a heck of a lot more money as a Class 3 because of the higher reimbursement.

Etienne Nichols: One of the things that I think about when I think of that is it's not just more expensive, it's an order of magnitude more expensive. And I didn't realize that the first one's free, so that is very helpful. I can definitely see that for sure. What are the advantages of PMA over 510? I've heard you talk about this a little bit on your webinar, and I love your approach to this, but I'd love for you to share the advantage of the pma.

Mike Drues: Yeah, great. So although there are some potential disadvantages, like higher regulatory burden, there are some very significant advantages to the pma. As a matter of fact, Eddie and I've worked on several devices where we were in kind of the gray area between Class 2 and Class 3. We could have gone either way, but the company opted to go to the PMA to take the higher road instead of the Lower Road, the 510k or de novo. And before I explain why, Edie, and let me flip it around to you, let me ask you a question. And that is, given a choice, if a company could bring the device, their device onto the market as a Class 2 or a Class 3, which path do you think the vast majority of companies would choose?

Etienne Nichols: They would go for the Class 2.

Mike Drues: They would go for the Class 2. Correct. And why would they go for the Class 2?

Etienne Nichols: It's perceived as easier. Market entry is a lot easier. I have a few disadvantages in my mind for it as well, but.

Mike Drues: Yeah, well, we'll get to that in a second. But. But you're exactly right, it is perceived as easier. But let's drill into that a tiny bit further. Who is it easier for? It's easier for you, but at the same time, it also is easier for your competition. So I've been in situations where, let's say not so hypothetically, you're working in a large medical device company, which is code speak for having a lot of resources, having a lot of money and so on, and your competitors are a bunch of small and startup companies, probably VC funded. Well, if you're a little bit ahead of them in the product development process and you get your device onto the market as a pma, as soon as they find out that their predicate device, and I know we're not supposed to use the word predicate in the PMA universe, but we'll talk about that in a moment when as soon as they find out about that their predicate device for their pma. Sorry, for their device, is a PMA that is going to immediately make them reevaluate their product development strategy, their regulatory strategy. It possibly might even make them close their doors and go out of business this afternoon. So this is an example of what I call competitive regulatory strategy. Using regulation as a tactical weapon against your competition and going in the PMA direction when a PMA may not entirely be necessary in some circumstances, could be very beneficial. Now, as you pointed out, there are some downsides of that as well. We have to take all of these things into account.

Etienne Nichols: You mentioned something using a predicate for a PMA device. Do you want to expand upon that a little bit? I'd love to hear what your thoughts are there.

Mike Drues: Yeah. So a lot of people say that you cannot use a predicate in the class 3PMA universe. I say baloney. I use predicates for class 3PMAs all the time. What it comes down to is what is your definition of a predicate? I'm not talking about the regulatory definition of a predicate meaning substantial equivalence, although we'll come back to that later, because there's also a way to do that. What I'm talking about is predicate in the engineering sense of the word. And What I mean by that, Elien, is in two ways. In terms of the testing of my device and in terms of the risk of my device. In other words, if I'm bringing a device onto the market, let's say the bare metal coronary stent, which is a classic Class 3PMA device, but there are dozens and dozens of bare metal coronary stents that are on the market that have PMAs. Well, even though my coronary stent might be a little bit different than the other coronary stents, it stands to reason that a lot of the testing that was done for those previous coronary stents is probably applicable to my device and the testing that I'll have to do. And similarly, when it comes to risk, and just as a reminder to our audience, Eddie and I happen to be a subject matter expert for FDA in a few different areas, one of them being risk. So if other coronary stents have risks, they might be, you know, the same or similar as risks of my device. So I use the concept of predicate all the time in the Class 3 universe, but not in the regulatory sense, rather in the engineering sense. Specifically, when it comes to the testing matrix and when it comes to the risk mitigation strategy, that makes sense.

Etienne Nichols: And in my past life, we would have called it a little bit of reverse engineering, not reinventing the wheel. But I know that's not exactly what we're talking about here. Similar, definitely. I agree.

Mike Drues: Content to the predicate, substantially equivalent.

Etienne Nichols: Yeah, to a certain extent.

Mike Drues: Yeah. Yeah, to a certain extent.

Etienne Nichols: If. If. Okay, so we talked a little bit about the predicate then. But what, what if a competitor's device is a Class 3PMA? Does yours have to be. Does yours have to follow that? Exactly.

Mike Drues: Yeah. Great question. And again, the textbook would say yes. Most regulatory professionals would probably say yes. However, I say no, not necessarily. Once again, average regulatory professionals know the rules. The best ones know the exceptions. So let's go back to that bare metal coronary stent example that I mentioned a moment ago. Bare metal coronary stents are all PMAs, no exceptions. But some people have asked me, Mike, is it possible to bring a bare metal coronary stent onto the market less than a Class 3? In other words, as a Class 2, as a de novo, or possibly even a 510k? And the answer is theoretically, yes. And here's how you would have to do it. You would have to come up with some reason, I. E. Your indications for use for putting your stent in the coronary artery for something other than Atherosclerosis. Let's say, for example, vasospasm. If you wanted to change the labeling of your stent to vasospasm, you could go to the FDA and you could argue that vasospasm is not a Class 3 claim, and therefore it's a Class 2 claim. And then that would open up the possibility to probably a de novo, which is a Class 2 or maybe a 510. But if you're the first one to do it, it's probably not going to be a 510. But the short answer to your question is it's absolutely not always the case that just because a device, a similar device to yours has been designated as Class 3PMA, doesn't necessarily mean that your device has to be designated Class 3PMA, especially if you can change the indication. And the other thing that I'll just remind you of, Edie, and as I mentioned before, I have several examples of devices on the market right now where the device is indicated, for one thing, used in one part of the body, and it's a pma, like for example, in the heart, whereas exactly the same device, for exactly the same indication is used in another part of the body, maybe the leg. And in that case it's a 510, primarily because the risk in the leg is lower than the risk in the heart. So, again, there are exceptions to every rule.

Etienne Nichols: At some point, I might be interested in getting even more detailed with that because of the I. I can see the CPT codes and different things like that really making a difference as far as. I don't know, there's a whole lot to think about there.

Mike Drues: Well, reimbursement is a whole other atom.

Etienne Nichols: Maybe that'll be next time. Okay, so I want to talk a little bit about clinical data.

Mike Drues: Yeah.

Etienne Nichols: Because, well, there's a couple different things. One of the things I was thinking of, and you can answer however you like, but when you were talking earlier about an HD humanitary device exemption first, then maybe a PMA later. I don't know what the requirements specifically are for hte vs. PMA, but I am curious what clinical data is required for a PMA and what are some of the advantages there?

Mike Drues: Well, first of all, let's just focus on the PMA for the moment, then we can come back to the HDE in a couple more minutes. So many people make the assumption that if I'm doing a pma, I must do a clinical trial, I must have clinical data. You can read every word in the regulation of the pma. You will not find that in there anywhere. There is no regulatory requirement that says if PMA, then clinical data is required. Similarly, in the 510 universe, a lot of people make the assumption that if you're doing a 510 that a clinical, clinical data or clinical trial is not required. And once again, you can read all of the regulation. And I encourage our audience to fact check me to make sure that I'm telling you what is true. But there's no regulation anywhere. I'm talking about regulation, I'm not talking about guidance. No regulation anywhere that says if you're doing a 510k, then a clinical trial is not necessary. So here's the way I would summarize it at IAN, most PMAs require clinical data. But notice I'm parsing my words carefully. I'm saying most. There are a few, granted, not many, But a few, PMAs that do not require clinical data. And then flipping back to the 510 universe for a second, most 510 devices do not require clinical data. Although again, notice I'm parsing my words carefully. I'm saying most, not all. There are a small number of 510s that are requiring clinical data. And for our friends in the class 2, 510 universe, that number of clinical trials for 510s is rapidly increasing for a variety of different reasons. But the better question to ask, I think, is whether or not clinical data is required for a PMA or even for a 510 is how much data is required, how many patients, over how long a time, how long, follow up, and so on and so on. Many people would consider me to be probably one of the more aggressive regulatory professionals around. It might be difficult for me to walk into the FDA and argue with a straight face that no clinical data is necessary for my device, especially if it's a new or novel device. But what I might be able to do is argue that a very small clinical trial is warranted as opposed to a much larger clinical trial. So I think a lot of people ask the wrong question of do I need to do a clinical trial or not? The better question is if I am going to do a clinical trial, what is it going to look like, how big, how long, how expensive, and so on. And then the other thing that I would mention, edien, is keep in mind that there are lots of reasons why a company might do a clinical trial, FDA or regulatory is one of them. But there are others. So let me ask you a quick question. If you see on FDA's website that a company did a clinical trial for their pma. Can you conclude that the reason why they did the clinical trial was specifically for the pma, that is for FDA or regulatory reasons?

Etienne Nichols: Well, and that's a good question. That's exactly what I wanted to say. A lot of people look at purely regulatory for market access, not thinking about market adoption. So I would, I would expect what the clinician themselves expect to see once it's on the market.

Mike Drues: Exactly correct. So, so just because, and I've seen many people make this assumption before they come to me, they're working on a, on a Class 3PMA device that's similar to something that already is out there. They say the other company did a clinical trial with X number of patients and so on. Therefore we have to do a clinical trial with X number of patients and so on. The short answer is not necessarily because. Although regulatory or FDA is one reason why a company might do a clinical trial, there are other reasons. For example, health economics, you know, getting or reimbursement, you know, getting CMS to reimburse for your device. As a general rule, CMS usually wants to see 10 times more data for reimbursement than FDA wants to see for their approval. You mentioned clinical adoption. You know, most physicians won't use a device simply because it's cleared or approved by the fda. They want to see more than that. So bottom line, we should be careful about assuming that just because they did a clinical trial and it's listed in their PMA doesn't mean that they had to do it. It doesn't mean that you have to do it.

Etienne Nichols: A lot of what we've been talking about is the requirements to get onto the market. But I know there are additional requirements once you're on the market, so maybe we could talk about that. What are the post market requirements when it comes to PMA? 510k or de novo?

Mike Drues: Yeah, great question. And again there are some significant differences, starting at the highest level, something that obviously Greenlight is very involved with and that is the quality management system. When you look at the qsr, the quality system regulation, they are totally agnostic of the classification of the device. In other words, the entire Qlik qsr. And this could be a topic of a different discussion, but the entire QSR is not dependent on Class 1 or Class 2 or Class 3. Maybe it should be. Some people have made that suggestion. But that's as I said, a topic of a different discussion. The question becomes to what level of detail, to what level of scrutiny do you apply the QSR requirements, obviously for a Class 3 device that's going to have, that's going to require much more detail, that's going to require much more rigorous scrutiny than say a class one device. So that's point number one. Point number two, when it comes into specifically the manufacturing as you and probably our audience knows, if you're submitting a 510k, there's no requirement whatsoever to tell FDA anything about your manufacturing process. It is not part of the 510 submission. It obviously it's a quality requirement, but it's not a regulatory requirement. When it comes to the de novo, it's a little more fuzzy because technically speaking, a de novo also does not have to include manufacturing information. However, as of just a couple of years ago, FDA now has the discretionary authority to ask for manufacturing information as part of a de novo submission. Finally, when it comes to a pma, your manufacturing information is required in a PMA submission. And the reason why should be obvious to anybody with an IQ of more than 5 because we're talking about, you know, more complex devices, more complicated pathophysiologies, higher risks and so on. And it makes no sense, especially in the Class 3 universe, to decouple the design of the device from the manufacturing process. Because if you design the device correctly, but if you manufacture it wrong, or if you design the device incorrectly and you manufacture the product correctly, either way the patient is going to die, right? So it doesn't make any difference. So you want to make sure that you address both of them. A couple of other things to mention in terms of post market change management is another big difference. As you know Eddie, in the Class 2 universe, in the 510K and de novo world, companies make changes to their devices all the time without notifying the fda, usually in the form of what we call a letter to file. And by the way, one of the biggest reasons why companies get in trouble with the FDA is because of change management or the lack thereof. And they do a terrible job with the letter to file. So I think that's very unfortunate. Suffice it to say, when we're in the class 3pm universe, I'm a little hesitant to go this far in this particular podcast, but we're getting close to the drug world in terms of making changes. I'm not going to go so far as to say that you cannot use a letter to file in the PMA world. Technically you can. It's much more common to do what's called a PMA supplement. There are some very special circumstances where you could do a letter to file, but again, we're talking zebras, not horses. What I would just simply say to our audience is, remember the Elmer Fudd in the Bugs Bunny cartoon? If you're considering a letter to file for a PMA device, be very, very careful because if you screwed up, you could be in a big world of hurt. And then the last thing that I wanted to mention in terms of major differences between post market requirements is in post market surveillance, as a general rule, the post market surveillance as well as the complaint handling requirements are more robust, more extensive. Some people might say more burdensome than a 510k or even a de novo. But once again, most of the time that's justified because we're talking about in the Class 3 universe in some cases, you know, life or death situation. You know, take the left ventricular assist device, that example I gave a moment ago. It comes down to very, very simple things. If your device works, the patient lives. If your device stops working or doesn't work, the patient dies. It's as simple as that. There's no gray area, right? So you have to be careful in that universe. And if you start to get, you know, notifications of complaints, you can't sit around on your, you know what, and you know, you know, you have to investigate them like asap. And just as an FYI for our audience, I do teach a three day course for industry on post market surveillance and clinical trials. If anybody is interested, you know, just send me an email. I'll be happy to send you the information.

Etienne Nichols: Cool. And we'll include his email as well. So if you want to reach out, you, you'll be able to get that. Okay, so maybe this is circling back to the beginning, I don't know. But you, you mentioned a few different examples, the bare metal stent for an example. But I do have a question. Are PMA devices, I mean, by and large, are they always new and novel? And you already, you kind of alluded to whether or not they should be reviewed equally. But how, how do you approach that in your, what does that look like in your mind?

Mike Drues: Yeah, great question, Eddie. And so many times people come to me and they say, I'm working on this newer novel device. And after describing it to me for 30 seconds or a minute, I quickly realized that, hey, there's nothing new or novel about this. So the question is, what is new or novel mean? I came up with sort of a litmus test that I published in one of my very first columns, probably about a dozen years or so ago now, and that is, if you think you're working on something new or novel, ask yourself the following three questions. Is there already regulation on this? Is there already guidance on this? And finally, is there already reimbursement for this? Let me repeat that once more. If you think you're working on something new or novel, ask yourself the three questions. Is there regulation on it? Is there guidance on it? Is there reimbursement for it? If the answer to any of those questions is yes, then I hate to burst your bubble. You ain't working on anything new or novel, because where would have that regulation or guidance or reimbursement come from if you were the first one to do it? So with that definition of new or novel, I would argue that the vast majority of PMAs are not in fact new or novel. I mean, again, the bare metal stent, you know, is an example. Yeah, there are minor differences in the design. Some of them are coil, some of them are a slotted hypotuber or whatever. But at the end of the day, they're all basically the same. They're all substantially equivalent. You know, they work in the same way. So most PMA devices are not new or novel. And so I have suggested over the years that maybe we need a, what I call a de novo like pma. You know, the big difference between the de novo and the, and the 510k, as you know, is de Novos are for Class 2 or lower devices without a predicate. Why should we create, Sorry, why should FDA treat all PMAs different? For example, and I used to design stents, you know, when I first started out my career, the very first coronary stents were brought, that were brought onto the market had a much higher regulatory burden than coronary stents bringing onto the market today. A much higher. Because we have a track record, we have a history of use, we have a good understanding of their risks and benefits and, and so on and so on. So why should FDA have to apply the same level of resources to evaluate a PMA for a bare metal coronary stent that's very similar to, you know, the dozens of them that we already have, as opposed to another PMA Class 3 device that is totally new, totally novel, totally revolutionary. So unfortunately, we don't have yet a de novo like pathway for the pma. But I've made the suggestion to the FDA many times. Perhaps, perhaps we might have one someday.

Etienne Nichols: Yeah, that is good suggestion. That is interesting to think about. And you kind of mentioned that not all PMAs are new and Novel. Maybe, maybe we can flip that a little bit. What. What would you say is new in the PMA world? And anything new or we don't have the de novo yet, but is there anything that's changing?

Mike Drues: Okay, so what's new in the PMA world? So, a couple of things. First of all, there was a proposal actually several years ago, and I'd be curious to hear what you thought about this. To let companies market a Class 3 device here in the United States without FDA approval. But instead, if they have EU approval, the question is. And then here in the United States, we would use post market surveillance here in the U.S. sort of. I guess it's repetitive, but retrospective post market surveillance to make sure that the new device is safe as we thought it is. But do you think that we should allow this at end? Do you think that we should allow if a Class 3 device. And keep in mind we're not talking about class two or lower devices, we're talking about class three, the most risky devices. Should we allow a company to market that device here in the US without getting a PMA from the FDA first? If they have approval in the eu?

Etienne Nichols: You know, giving you a direct answer, maybe playing a game I don't want to play, but I'll give you a nuanced answer. And that is, I feel like quality should be quality wherever you are. Yeah. You know, I. But that being said, I have my United States independent spirit. Well, we better check it out ourselves. So there's a few different things that I would, I would want a PMA light. I think. Sure. That what they have, what they've done is suitable to what we would expect to be done.

Mike Drues: I love your phrase PMA light. And by the way, you know, not to wave the flag here, but coincidentally we're, we're recording this conversation on election day. So who knows what's gonna, you know, what's gonna change, you know, depending on what happens. But we won't go there.

Etienne Nichols: Sure.

Etienne Nichols: PMA rule, that's really interesting. I had not heard of the six year rule either, so this has been very enlightening episode for me and I hope it's been for those listening as well.

Mike Drues: And one last thing that I just wanted to mention before we wrap this up at the end, and that is you and I did a podcast. I think it was our last podcast that was just recently published on predetermined change control plans, the PCCPs. And coincidentally I'm doing a webinar for Greenlight next week on the PCCP in the PCC guidance. It is totally agnostic of the classification or pathway to market, so it's going to be an interesting thing to see. Can we use the pccp in the class 3PMA universe? In other words, to put it in regulatory terms, it would be kind of like getting a pre. Sub. I'm sorry, a pre. Let me say it again. It would be kind of like getting a PMA supplement approved in advance as part of your original PMA submission. Yeah, I think it's going to be interesting. I personally have not tried a PCCP yet in the PMA world because although I do work on a number of PMA devices, the PCCP is still a relatively new kind of a pathway, but I would love to be one of the first or even the first to try because by my reading of the PCC guidance, there's nothing that would necessarily preclude me from using the PCCP in the Class 3 universe. I just wanted to bring it up here. Even though there's not precedent for this, at least not yet, it is a possibility and it's something that companies should consider. Yeah.

Etienne Nichols: The PCCP is even codified now in the 21 CFR. I can't remember exactly what section it is, but since the Omnibus act, it's been in there specifically for PMAs.

Mike Drues: Yeah. And as a regular consultant, you know, I have a fixed amount of brain space, a fixed amount of storage, so I don't bother memorizing the, you know, the numbers of the code. More important is for people to understand what the code says.

Etienne Nichols: Right. It is interesting if you do do the first, you know, maybe we'll have to talk about that one of these days.

Mike Drues: So that would be. I would love to.

Etienne Nichols: Okay. Any other things that we need to cover before we wrap it up? Any other thoughts?

Mike Drues: Yeah, so just to wrap this up, and I think this has overall been a really great discussion of the pma. If you come away with only a couple of things, I hope there are these. First of all, don't be afraid of the big bad pma. Even though, as we've talked about, it does overall have a regulatory burden, it does have more time, more cost, more risk, all those things, in most cases it's justified because we're talking about more complex devices, more complex procedures, pathophysiologies and so on and so on. And just a matter. Just imagine, Adien, if the drug world took the same approach as the medical device world, we would never have a new drug onto the market ever. So I think it's sort of a convenient excuse that the medical device world uses sometimes not to use a PMA, but instead to only focus on 510ks and de Novos, because in the drug world that's not even an option.

Etienne Nichols: And can I have one thing on that? So having talked to a lot of investors and M and A at Strategic, they would rather, they would rather acquire a Class 3 medical device than a, than a 510K for the same reasons you put on, for competitive reasons and so on. And also that the little guy, quote unquote, did the work for them. So they got, you know, close to being ready. That's my understanding.

Mike Drues: So on your experience, because this is interesting. When the, when they get acquired, these are already when they had the PMA approved. Is that correct?

Etienne Nichols: Yeah.

Mike Drues: Okay, so that's a little different scenario than what I was thinking because in that case, most if not all of the risk has been greatly mitigated because they already have the pma. In my experience, when before the company has the pma, especially if it's a small company or startup trying to get angel or VC money, as soon as you mention the possibility of a pma, then basically they say, this conversation is over. Don't let the door hit you. And you know what, on the way, on the way out. And I think that's tremendously important because it's one thing to look at the devices that we're developing and that we have on the market. It's another thing to look at the devices that we're not developing and why we're not developing them. There are a number of very significant devices that could benefit a lot of people that are either not being developed or in some cases not being developed very quickly because it's so difficult to get the funding. Because it's a, it's a, It's a Class 3. Right. And then the last thing, just to reiterate one of the comments that I made earlier, and that is some of the companies, including some of the largest medical companies on earth that I work with, they, as a matter of company policy, will not develop, will not pursue, will not, you know, bring to market any device that even might be a Class 3 EMA. And I think that's just very unfortunate thinking. I mean, can it, can you, as an engineer, Edien, can you think of any way to hamper, you know, product development and putting those kinds of limitations? It's kind of like when companies tell their R and D engineers only make a change to our device to the point that it could be handled as a letter to file. Do not cross that line where it would require notification of the FDA by a special 510. Once again, I understand why they're concerned, but can you think of a better, more effective way to hold us back than for companies to impose those kinds of limitations and their R and D engineers? Maybe it's because I started out in this business 30 years ago as an R and D engineer, but when I hear those kinds of policies, it just makes my blood pressure go through the roof. It's just, you know, I, I'm tired of hearing companies and this industry in general use a FDA as an excuse. Well, we would onto the market if fda, you know didn't make us do this, that and the other thing. I just. Sometimes that's true but I think it's just being over overly used excuse. That's just my opinion. Maybe some people might disagree.

Etienne Nichols: Well and if anyone out there does disagree, love to hear it. I'm sure Mike would love to hear it as well. Hit him up on LinkedIn. Use the email in the chat or in the show. And yeah, thank you so much, Mike. Really appreciate you coming on today. This is a lot of information so I hope, I hope a lot of people got a lot of good out of this and we'll be sure and share all of the things that we mentioned in the show notes. So everybody, thanks so much for listening and we'll see you all next time. Take care.

Etienne Nichols: Thank you so much for listening. If you enjoyed this episode, can I ask a special favor from you? Can you leave us a review on itunes? I know most of us have never done that before, but if you're listening on the phone, look at the itunes app. Scroll down to the bottom where it says leave a review. It's actually really easy. Same thing with computer. Just look for that leave a review button. This helps others find us and it lets us know how we're doing. Also, I'd personally love to hear from you on LinkedIn. Reach out to me. I read and respond to every message because hearing your feedback is the only.

Etienne Nichols: Way I'm going to get better.

Etienne Nichols: Thanks again for listening and we'll see you next time.