#416: Unpacking Common FDA Compliance Gaps: Pre-Market vs. Post-Market Realities

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: Hey everyone. Welcome back to the Global Medical Device Podcast. My name is Etien Nichols. I'm the host for today's episode. With me today is Mike Drewes, a familiar voice on the podcast.

And today we want to talk about compliance issues that are common compliance issues for medical device companies and maybe how to overcome those.

Recently, three medical device senior operatives or operations officers from the FDA's offices of inspections and investigations spoke at a conference about the most common issues FDA encounters during the pre market review of medical devices.

So Mike, I wonder if, do you want to kind of talk about what they said? Maybe we can dive in here?

Mike Drues: Yeah, absolutely, Eddie. And first of all, as always, thank you for the opportunity to have this discussion with you and our audience.

In the interest of full disclosure, I did not attend this presentation myself.

So this discussion is based on the RAPS article as well as I do have some friends that attended firsthand and they shared with me some of their observations as well.

Second thing I just wanted to point out, especially for my FDA friends, is that we are going to be following CDRH's policy, which I'm adamantly against,

about not naming any specific names of individuals even though the names of the three people that participated in this discussion for FDA are publicly known. If anybody in our audience has ever participated in a pre sub meeting,

for example, you know that FDA prefers in the meeting notes not to say Dr. Smith comma, FDA said, but rather FDA said.

I find that tremendously unfortunate because I stand behind what I say when I give a customer a recommendation. I think that the folks in FDA should do the same thing anecdotally.

Edin, do you what do you think of that policy of not naming names?

Etienne Nichols: Yeah,

I guess I could see maybe both sides of it. On the one hand, I certainly think you should stand behind what you say. For example, if I'm at a medical device company, I remember early in my career as a manufacturing engineer when I first started at a company, the VP of quality came out while I was at the printer and he said,

hey, my name is so and so. We're the quality department. Our goal is to make sure that you are able to understand and follow all processes and procedures so that you don't get in trouble.

Because when you sign your name on a document, that is you and your name. And we want to bet make sure you're supported so that you don't sign anything you shouldn't and so on.

And that meant a lot to me. And I, I feel like potentially should be the same on the other. I'll just throw one other because if I look at it from the other direction, that carries a lot of weight for me in my career if I feel as though I am speaking for the company or in this case the fda.

So I don't know that I'm going to be able to change this. I feel like I have a little bit of weight on both sides. That's not good to ride the fence, but here I am.

Mike Drues: Good point. Like all issues, there's, you know, pros and cons to both sides. But I just, I just personally have a problem with that policy. It's kind of, you know, coming from a medical background, it's like if you needed surgery and there's a report written of, you know, the surgery afterwards,

do you want it signed by John Smith, M.D. or do you want it signed by House Surgeon or something like that?

Yeah, anyway, that's just sort of a tangent. So let's come back to the, to the, to the topic at hand and that is the common issues that these three folks from FDA identified as potential problems during the pre marketing review of medical devices.

They listed lack of documentation for software changes,

design creep and marketing beyond authorized intended use. We'll talk about these individually in more detail. But again,

lack of documentation for software changes, design creep and marketing beyond authorized intended use. And before we talk about them individually, edien, my question is, are these really pre market issues?

Because to me, none of these are pre market issues. For example,

how can you market beyond authorized intended use when your device is not yet on the market?

Right. So how do we connect those dots? That makes no sense to me. What does a pre market or, sorry, what does design creep or design change mean? Pre market?

Once again, you do not have a device on the market yet. Now if you're talking about a device that's already on the market,

which would be a post market change and you want to make a change to that device,

that's under the category of change management,

which we've talked about many, many times, it's a very common source of problems for companies to get into with the fda.

Design creep. They talk about it,

as we'll say, in the context of what we call predicate creep.

And finally, software changes. Whether you change,

you know, your device, if it's a software or a physical widget or what it doesn't matter if you're changing it pre market, you can do anything that you want because it's not on the market yet.

So I don't know. Edien, do you see a different way that this can be spun as pre market changes?

Etienne Nichols: When I think about the documentation, pre market review issues, yeah, when I think about the documentation issue, I mean I suppose that one could certainly could be a pre market review if you haven't done all of your homework, all the things necessary.

But regarding design creep, that's more of a project management or company issue prior to commercialization. So yeah, I'm with you on this being really being post market issues.

Mike Drues: And just one last thing, in terms of the documentation, obviously you are correct, we are required to have certain documentation regarding the design, even pre market,

whether it's software or anything else. However, that's more of a quality requirement.

That would not be a regulatory requirement in the sense that you do not have to include a DHF or any of that kind of stuff stuff in a 510 submission.

You would expect to have it, you know, in a manufacturing and inspection. And even if it wasn't a quality requirement, I just think it's, you know, it's common sense, it's prudent engineering, but it would not be required in a, in a regulatory sense.

Etienne Nichols: One question about that because I'm not as adept with Class 3 medical devices. Are there certain aspects? I mean we're obviously the bolus of devices are Class two that we talk about with Class three.

Are there some documentation issues that are more of a regulatory requirement?

Mike Drues: Yeah, good question. And Ian, there are. The Class 3PMA or HDE universe is a different universe in many ways. However, what I would say in brief is that the general documentation requirements are the same whether it's class three, Class two or even class one for that matter.

Because as you know,

the QSR is largely agnostic on class,

agnostic on class. In other words, it doesn't matter whether it's class one, Class two, Class three, the basic requirements are the same. The thing that really differs however is the level of detail that go into those documents.

So for example, if you have a DHF for a Class 3 device,

it should, without even reading it, it should be much longer, much more detailed, much more explanatory than say a class one device. Yeah, and that should make sense for.

Etienne Nichols: All the obvious reasons, more risk mitigation, et cetera. Yeah.

Well I want to ask you then.

So pre market, post market,

Regardless, in your 30 years of experience working in the medical device industry. Would you agree with what's what the FDA said about these being the three most common issues or what are your thoughts there?

Mike Drues: Yeah, good question. And I would say yes and no. Or in the regulatory vernacular, it depends.

Certainly these are three of there's three common issues that FDA has identified and is worthy of talking about. And I would also point out, Etienne, that these issues have been around for a very, very long time.

So there's nothing new here.

But on the other hand, there are a heck of a lot more what I would consider common issues as well that I would add to the list, for example, and again, it depends on whether we're truly talking pre market or post market.

So let me, for the sake of clarity here,

divide them in two. On the pre market side,

remember one of my favorite statistics is about for 510 universe and the vast majority of our audience are working on 510 devices.

38% of 510s that are submitted to the FDA, about 38% of them are rejected on administrative review,

which means that they're missing a section or a signature or something like that.

And that's certainly a common issue.

Also on the pre market side, I would say that once the administrative review is over and you get into the scientific or the substantive review,

you get a lot of common issues there,

not the least of which is FDA not agreeing that your 510 your device is substantially equivalent and you get a not substantially equivalent notification.

That's a very, very common issue. Remember, some more statistics for you, and we've talked about these in other podcasts and webinars as well.

About 75 of 510s are rejected by the FDA first time out of the box. That number fluctuates a little bit, but it's pretty constant over the decades. And of those that are rejected, almost 85% of them are rejected specifically because of substantial equivalence or the lack thereof.

So that's a couple of common issues on the pre market side. Moving on to the post market side, and once again I've done some webinars and even a recent sorry podcast and even in a recent webinar on this, the top three most common reasons why companies get 43 in warning letters from the FDA post market are CAPAs.

That's a little over 12%, about 12.5%.

Design controls, that's also almost 12 and a half percent, and complaints. That's about 10.5%.

So collectively CAPA's design controls and complaints or complaint handling represents about 35% of all of the reasons, the most common reasons why companies get in trouble with the FDA on the post market side.

So I think that the three issues that FDA is talking about in this particular presentation are certainly important, certainly valid common issues, but they are by no means the only combination.

Etienne Nichols: Yeah,

and I wanted to dive into each individual issue at some point here. But what do you think the root causes of these problems? Or do you think they all have their own unique, separate root cause?

Mike Drues: Yeah, great question. I actually think there's, there are some common, there's a common root cause or maybe a couple of common root causes. But first, Eddie, and let's put things in perspective.

FDA points out, and I strongly agree,

the vast majority of medical device companies are largely compliant. In other words, they do what is required to do.

They do what they should too. But these common problems that we're talking about are a big source of problems for companies,

at least certain companies.

One of the folks at FDA said this is a quote, this is a topic that to me seems like it should be straightforward,

but it's not. And it's definitely something that we see problems with in the field.

So FDA recognizes that this is a problem. And by the way, that the reason why I bring this up, Edian, is because just a few Weeks ago on March 22, I did a webinar for Greenlight called CAPA vs.

PACA and coincidentally I mentioned that Capa, as I said a moment ago, was the top reason for FDA warning letters. And Manu and I also said that manufacturers seem to be making the same mistakes over and over because CAPA's complaints and design controls have been the most common sources of problems for companies consistently for Almost the last 20 years.

Almost the last 20 years. But anyway, the reason why I bring that up is because I got some an email from one of the participants afterwards who seemed to imply that I put all the blame on industry and asked what I thought was a valid question.

What about the other side of the picture? In other words, what about the regulators? What about specifically the FDA and what this person said, quote,

regulations required to conduct human factors testing, for example, to analyze human capabilities and limitations.

Why doesn't the FDA conduct its own human factors testing to see why companies seem to make the same mistakes over and over again?

Perhaps it's the regulation that needs to be clarified simply or simplified as well.

So before I give my thoughts on this person's comment, and I do think it's a very legitimate comment,

what do you think about that idea? What do you think about putting some of the Blame on the FDA for the way the regulation is written. And specifically,

maybe FDA should do their own testing to figure out why we in industry can't seem to figure it out.

Etienne Nichols: You know, it makes me think of emdr,

because there's a debate about whether emdr, because if you're on the other side of the pond, maybe you're thinking, well, we're safer because we have a more complex regulation.

And that's debatable. You know, I suppose the question I have for those companies though is has this new regulation,

it's obvious, created a lot of new work for those companies to get up to speed and be compliant, but I wonder if any devices are actually safer due to this additional regulation.

So I guess this is the roundabout me way of saying, my way of saying,

I would imagine that there probably is some aspect of the regulation in the FDA as well that may not necessarily make devices safer, but because the regulation is there, these companies are non compliant, which makes them look less safe than they truly are.

Is it? So I guess let me divide this,

my observation of the regulation into two categories.

Are these companies non compliant? Whether it's capa, design review, whatever, are they non compliant due to the admin side of the regulation or the scientific side of the regulation? And that takes a little bit more detail to get down into there, but people probably would rather hear what you had to say with my quantification.

Mike Drues: No, not at all. I value your opinion just as much. I don't want to go too much of them on a tangent here, but I like the way that you divided it more on the administrative side, which I would consider to be filling out the forms, dotting the I's, crossing the T's.

And let me be honest,

I could care less about that. And as a regulatory consultant, that might sound like heresy to some people. But one thing I've learned, not only as a professional biomedical engineer, but of being in this business now for over 30 years, is there are hundreds and hundreds of things that can influence the safety and the efficacy of any medical device.

But one thing that I will guarantee will never be on that list is the form that we put the information on.

And one of my frustrations is sometimes people in companies and at the fda, they seem to be more focused on the form rather than the content, the substance. And I find that unfortunate.

On the other side, when it comes to the scientific stuff,

that obviously is more important. And again, I don't want to go too much off on a tangent, but let's put it this way, Eddie and I have never, ever assumed that safety or efficacy of devices is, or drugs for that matter, is, is proportional to the amount of regulation that we have.

In other words, the more regulation that we have,

d enough to remember prior to: 1997

we had no design controls, we had very little regulation, or certainly less regulation than we, than we have today.

And yet somehow we were able to get reasonably decent medical devices onto the market.

Fast forward nearly a quarter of a century and we've got tons and tons of regulation. We've got tons and tons of regulatory professionals, and I use that word in air quotes, both in companies as well as at the fda.

The question is, and I'll leave this as a rhetorical question, Eddie, and maybe we could talk about this a different time. The question is, with all this additional regulation, with all these additional regulatory professionals, are our devices any better?

Are, you know, are they safer? Are they more effective? But anyway, we'll leave that as a, as a rhetorical question. So my response to this person's comment, and again, I really appreciate this person sharing their views with me, even though they might be a little bit, you know, different or contradictory with regard to the FDA's responsibility.

I just want to remind you and our audience that I have perhaps not a unique viewpoint, but a very unusual viewpoint in the sense that I work for both companies as well as the fda.

So I see these issues from both sides of the fence.

That said, while I do certainly blame FDA for certain things,

I do not expect FDA to tell me what to do or how to do it. If they were in the business of that, then why don't they just go out and develop their own products?

Right? What do they need companies for?

And another thing that I would say is you meaning our audience, that the companies and the people in them, you should know a heck of a lot more about your device than the FDA ever will.

Yes, FDA might know a little more perhaps about some of your competitors devices, although you should know about those as well. But if there's a situation where FDA knows more about your device than you, that's a problem.

Expecting FDA to tell us what to do is kind of like treating them as my school teacher, you know, and it automatically puts me in a, in a position of subservience, if you will don't get, don't miss my message here.

I have a huge respect for the FDA and the job that they do. As one of my friends who used to be a senior reviewer, FDA likes to say a physician can kill patients one at a time, but an FDA reviewer can kill patients thousands at a time.

So there's nobody that has a greater respect for the job and the responsibility that they have. But on the other hand, I don't worship them.

I will, I will. When I, when they say or they do something that I agree with, I will be the first one to say that. But when they say or they do something that I disagree with, I will be the, the first one to do that.

Regrettably, Eddie, and, and this is my opinion, some people might disagree with me, but that's okay. We have people in our industry,

maybe many people in this industry,

quite frankly, who do not know what they're doing and need to be told literally what to do. Step one, do this, step two, do that, and so on. And again, in my opinion, edien, people like that, they shouldn't be working in this industry or they should go to school to learn those things.

Again, I'll give you another real quick anecdotal example. I was talking to a new company. This was a couple of years ago. They were working on a permanent implant, a device that was going to go inside somebody's body for the rest of their life.

And I was going down my mental checklist of you done this testing? Have you done that testing? And we got to the topic of biocompatibility.

And as you know, Eddie and I happen to be a subject matter expert for FDA in a few different areas, one of them being biomaterials and biocompatibility. And I said, where are you on your biocomp testing?

And they looked at me and they said, mike, what's biocomp testing? What's biocompatibility?

Now, one would like to, you think, you know, you're laughing, Eddie, and you think I'm joking. I'm being 100% serious.

This is a company who is. Doesn't matter what the device is, but it was going into somebody's body as a permanent implant for the rest of their life. Or technically, permanent implant means greater than 29 days.

But anyway, it doesn't matter. And you would like to think that somebody doesn't have to be an MD or a PhD in biomedical engineering or even a subject matter expert in biomaterials to think that, gee, maybe we should consider what is going to happen to this device, after it's been in the body for some period of time,

is the body going to react with it? And if so, how? I mean,

anyway, what can I say?

And one other thing that I'll mention, Eddie, and then I'd love to hear your thoughts on all of this is I said to this person in my response, I said, consider this.

What if the FDA did not exist?

In other words, let's pretend for the moment that there was no fda.

Sooner or later,

you might be on the receiving end of your device. What would you, Edian, or me, Mike, or somebody else want to see in terms of benchtop testing, maybe animal or clinical testing,

so on and so on.

And finally, and I've said this many times, Eddie, and I really wish that I worked in an industry where we wouldn't need the fda, where we did the things that all of us or most of us know that we should do without having Big Brother or the police or ever telling us that we have to do things.

You know, regrettably, Eddie, and I think that.

And I do not take pride in saying this about our industry, but I'm just simply being honest.

I think we have come to use regulation as a convenience excuse,

not to justify what we do, but also to justify what we don't do.

And one of the things I love about working as an expert witness in medical device product liability cases is attorneys don't want me to talk about what FDA did or did not want the company to do.

What the attorneys want me to talk about is what they should have done, regardless of whether it was required or not by the fda.

So there's a lot of issues that are sort of piled in there, but I'll end this section with this part.

One of my favorite regulatory mantras is if the regulation makes sense,

we shouldn't need it.

If the regulation doesn't make sense, we shouldn't have it.

I'll say this one more time, and then I want you to chime in. Edien. If the regulation makes sense,

we shouldn't need it.

If the regulation doesn't make sense, we shouldn't have it. I. And maybe I'm unusual or maybe even unique. I do not need FDA or guidance or regulation or anybody else to tell me what to do.

As a professional biomedical engineer, I know what I need to do. I will use the regulation and the guidance as a backup just because. Just so I don't forget something.

But other than that, I know what to do. Why? Because I consider myself to be a medical device professional,

just like a Surgeon is responsible for knowing not just how to do the surgery, but what to do if this happens or that happens, what the alternatives are. And if the surgeon doesn't do something,

they are held accountable. I think medical device professionals should be responsible and should be held accountable as well.

What do you think?

Etienne Nichols: Well, okay, so I'm just going to provide a little lateral thinking here just for a moment, if you'll bear with me.

I used to race motorcycles in Hallett at the Hallett Racetrack in Jennings, Oklahoma. And I had a motorcycle that I knew how to go around a track at a certain speed.

Now people ask me why doesn't the FTA tell me exactly what to do? And this, this, this and this different situation. There's certain vague aspects to the regulation. And I told them the FDA is not going to give you a 45 mph speed limit around a 45 degree turn.

What they're going to say is it's a 45 degree bank with the surface friction, with the wind coming out of the north, et cetera. If you're riding a motorcycle,

you might be able to double what's on the speed. What's on that speed sign. If you're, if you're driving a semi truck, which I actually had a Class A CDL at the time too, you might need to cut it in half and you might need to go slower if you're,

if. So if you're developing a Class 3 medical device or if you have a Class 1, there's different requirements from a consumer perspective,

from you as a company perspective.

And yes, I'm with you, we should live in a world where you don't need speed limit signs because people have the experience to drive what they are driving, but they do not do that.

So I am thankful that they're there.

Mike Drues: Well, first of all, Eddie, and I love the metaphor, not so much on the speed limit science, but the previous part about the motorcycle versus the truck. My question to you though, Edian, is where should those guidelines come from?

Should they come from the company?

In other words, should the company know that already?

Should they come from the fda? Maybe they should come from both.

Where do you think they should come from?

Etienne Nichols: I do think it's a both situation.

What they're looking at is they're trying to meet. I think it's a Gaussian principle. I mean, you can't always handle the long tails, which is why we have that class three and de novo process for special controls that the company is going to work in conjunction with the FDA to develop Right.

So as a general rule, it comes from the industry,

and then the FDA recognizes what is standard. And I think we use that word so often in this industry, we forget it actually means standard is the basic level that everybody should meet.

And it's okay to go above and beyond the standard.

But I don't know if that's answering your question, but I think it's this one feeds that one, which feeds this one, which feeds that one.

Mike Drues: Yeah, I think that's a good response. I think they're definitely interrelated. And I think in that sense, it's a good thing because it's part of our check and balance system. In other words, if the company forgets one thing, then maybe the FDA will pick it up.

On the other hand, if the FDA forgets one thing, then maybe the company will pick it up. So I'm fine with it being sort of both sides, what I would say.

And then we can move on to the examples that we wanted to talk about for these three common problems. What I would say, though, is this FDA can ask a company to do anything that they want.

Literally anything that they want. So the facetious example I often use is,

before I begin my presentation, FDA could say, mike, we want you to stand one foot and jump up and down.

I mean, literally, FDA can ask companies to do anything they want. Doesn't mean that the company has to do it. Now, as my wife would be the first to say, you have to pick your battle.

Some things are worth fighting over. Some things are not.

However, there have been many, many times where FDA has asked me to do something, a form of testing, for example, that as a professional biomedical engineer, I thought was not necessary.

And if it was a trivial test that we could do quickly without much money or time, I would say to the company, let's just do it and get it over with and, you know, keep our political capital for.

For something worth fighting for. But if it's something. I had a bio comp test that that FDA wanted us to do, which is a biocomp expert I did not think was necessary.

And if we did this test, it would take three months and cost, you know, well over $100,000 to do. That's where something where we drew our line in the sand and we pushed back.

So FDA can do anything that they want. But before I say, okay, Mr. Or Mrs. FDA reviewer, you are God, so we will do anything that you tell us to do,

I'll say, can you please explain to us why you're asking us to do this test?

Yeah, I think that's a very, very fair question.

Now, if they respond and say, well,

we're aware of a similar problem happening to another device out there and we want to make sure that that same problem doesn't happen to you,

absolutely, that's fair game. That's FDA's doing their job. And I would be ticked off if they didn't do that.

On the other hand, if they just come back, and I've seen some reviewers basically say something along these lines. If they come back and say, well, we're the fda, we can do, you know, we can ask you to do anything that we want.

I'm sorry, that just doesn't.

Oh, yeah. And in one situation, this was actually not here in the United States. It was in a different regulatory authority I was dealing with, where the regulatory reviewer agreed with my position that this testing, which was required in their regulation is unnecessary.

But basically what this person said is,

this is what the regulation says. I agree with you. It's not necessary, but you got to do it anyway.

Yeah, I mean, at that point,

I would say, with all due respect, but I do not have respect for people like this.

At that point, I knew I was dealing with nothing more than a bureaucrat who knew that as long as he followed the regulation, he wasn't going to get fired.

Never mind if a test is not necessary, never mind if,

God forbid, harms happen to a patient, as long as he's following what the regulation or the guidance or whatever it is says, he's not going to get fired. He's doing his job.

And in my opinion, edien, that's one of the things that gives regulatory a bad name.

Etienne Nichols: Yeah, yeah, absolutely. Those are good examples. Well, let's jump into some examples about the issues that we were discussing a little bit earlier.

Provided the software being modified, post clearance, et cetera.

Mike Drues: Happy to do that, edien. So, first of all, let me just say,

unlike a lot in a lot of podcasts and webinars and even what the FDA does,

they speak in generalities and platitudes and they will rarely, if ever, mention a specific company name or a specific device. And I find that to be very unfortunate for those in the audience that have seen any of my work, you know, that oftentimes I use specific devices from specific companies and I name them.

In some cases, these are products that I've been involved with in the past, in other cases not. But as long as the information that's being presented is based on publicly available sources,

I have absolutely no problem doing that. And by the way if we're going to call ourselves medical device professionals at ian,

we should be responsible for what we do in not just in the, you know, in the context of the relationship between the company and the fda, but in the, in the broader context as well.

So how about if we start out with one of the three categories that FDA talked a bit about and that is design change and design creep. Does that sound good?

Sure.

Etienne Nichols: Well, yeah, let's talk about it.

Mike Drues: So how can design change or design creep get companies in trouble with the fda?

Well,

some of the things that they talked about is if a design change impacts a medical device's usability or safety or efficacy,

it warrants at least a review of the device.

If that's not a statement of the obvious, I don't know what is. But we've talked about this so many times.

Depending on the review,

if you're not submitting a pre market authorization, this is the FDA speaking now, not me.

The only thing that they can recommend is to justify and to document really concrete that the decision,

the decision and the basis of the decision.

So when we, meaning fda, comes in,

the company can explain it to them.

My response is duh. I mean, this is all under the general context of change management. So assuming that we're talking post market now, because pre market, I have no idea what this means.

But, but post market, if you have a device on the market, whether it's software, whether it's a physical widget, I don't care what it is, you want to make a change to that device.

If It's a Class 2 or lower device, you basically have two options.

You can do a letter to file, which means that you don't notify the fda, or you can notify the FDA with usually a special 510 or sometimes a traditional 510 in the PMA.

I'm sorry, in the Class 3 universe, you have less flexibility. You can still use a letter to file in a, in a Class 3 device, but it's much, much more limited.

Typically what would be required there is a, is a, is a PMA supplement.

So at the end of the day, nothing that FDA is saying here is new. And even more unfortunate, it's all common sense. Even if they were to pick out some examples, and this is something that I do in my webinars all the time, pick out some examples in your own guidance document that talks about,

you know, okay, you have a certain kind of a device,

then you want to make a certain kind of a change to it.

Is this something that requires Notification of the FDA or not, and why,

what kind of testing would be necessary to demonstrate that it does not impact safety, efficacy of performance, usability, all those kinds of things. To me, Edin, that kind of example is much more useful to most people than just making a very general broad statement like if you're going to make a change to your device,

maybe you should think about it or document it or something like that.

Again,

you're laughing so you appreciate my sense of humor.

Etienne Nichols: I'm laughing from experience as well. So I experienced FDA guided inspection where we received three 483s and most of them, or at least a lot of it, was the lack of justification on some of the change orders, the engineering change orders, ECO DCOs.

And so I learned to appreciate that none of them were mine, thankfully. But we changed the evaluation on all change management after that. And I think a lot of companies don't do a good job with that.

And I was surprised at how terrible we were at it because I didn't have a lot to compare it to. I don't bring up greenlight guru our software very often, but we actually have an evaluation form in our software that forces you to go through those.

We can't force the engineers to be honest, but we force you to think about it. Is the product impacted? If you say yes,

are design changes required?

Is verification and validation required? Are processes impacted? Is risk affected? Are regulatory updates required? It forces you to walk through those, either justify or give a rationale as to why.

And I think more companies need to think about their change management process.

Mike Drues: But yeah,

no, and I strongly agree with you and obviously your software does a really good job of doing that. I take generally the same approach with my customers, although I'm sure I probably push harder than your software does because I really want them to justify.

Don't give me a yes or no answer. I want to know why, you know, and anyway. But coming back to what some of the things that FDA said in this presentation, which I think is all good advice, but it's very high level, it's very general,

they specifically brought up software.

Now, we all know that software is becoming more and more important in the medical device industry,

either in devices that contain, you know, physical components or now SAMDS software as a medical device. What I find interesting, Eddie, and is that a lot of people think that software, a medical device that's software is so different than any other medical device.

And you know what,

obviously there are some differences, but largely they're the same. They're exactly the same in terms of how you handle things like testing and change management and so on. And so with that background, the reason why I bring it up is because FDA says the biggest issue stemming from this,

referring to software,

comes when a software engineer does not have a trigger in their change management system to alert their regulatory team in the company when a change should warrant a review.

I think pretty much any change, unless it's an absolutely trivial change, and we can quibble on what trivial means, but absolutely any change should warrant an internal review,

for instance. And again, this is back to what FDA's saying.

Changes to software requiring a review can sometimes be labeled as an upgrade, an update, an improvement, a bug fix, and so on. And here's a direct quote I've seen, meaning this FDA person saying,

I've seen at firms, they're software engineers,

they're focused on fixing that bug,

and once the bug is fixed, their goal has been accomplished.

In other words, they're done, the bug has been fixed. I've seen a lack of trigger with the regulatory staff coming in to see if that software bug and to change main tools, it would require a review.

In other words, the important thing here, Eddie, and I'm going to simplify this tremendously because I think they're making this much more complicated than it, than it needs to be.

You have a piece of software, you have a bug,

you fix the bug, the bug is removed.

Is your job done?

Absolutely not.

Now you have to ask yourself the question overall, in sort of a holistic fashion,

does your software still work? Is it still safe, effective?

Has the usability been impacted or any of those things? Just because you remove that bug doesn't mean that you haven't necessarily created some other problem that didn't exist before.

You know, it's sort of the law of unintended consequences. You know, our intention is to fix this one problem,

but in spite of our best intentions to fix that problem, we've inadvertently created another problem. And Eddie, and sometimes that other problem is bigger than the first problem that we had to fix.

This is one of the most basic tenets in the design controls. You know, this is goes.

This is, you know, in that: 1997

It doesn't need to be updated.

Good regulation is agnostic of time, and it's also agnostic of technology.

Anyway, I'm sorry to be going on a bit of a soapbox, but yes, there are differences when it comes to software But I think the similarities by far outweigh the differences comparing software to other kinds of devices as well.

Whether they be in vitro diagnostics or hip implants or whatever the heck they are. If you understand as we've talked about many times before, Eddie, and the regulatory logic, that's the most important thing.

Etienne Nichols: Yeah,

no, I agree. If the only reason the regulation should be streamlined for software because they can move faster. I mean why would you not streamline it faster if you could 3D print a doc 3D print instead of have to go through multi cavity, you know, updates, you know that take a long time.

That's, that's really the, the argument there. And it doesn't really hold water. I don't think so.

Mike Drues: And just imagine Edin, if our friends on the drug side of our, of the industry could use that same lot logic.

Etienne Nichols: Yeah, yeah,

it's easy to change a recipe.

I mean, well it could be.

Let's, let's move on. I know we're kind of coming up against the clock here a little bit. What is marketing beyond authorized intended use? What are your thoughts there?

Mike Drues: Great question. So first of all FDA says it's becoming an increasingly big issue that companies are marketing their devices beyond authorized intended use. So a moment ago I, I gave my FDA friends in this presentation a little bit of a hard time because they didn't use specific examples.

Let me use a very specific example. I'm going to specifically name the company and the product and in the interest of full disclosure, this is not a company that is a customer of mine.

This is just based on publicly available information.

So just last year and we can cite the source as part of the webinar resources if we want to.

The company came out with a press release.

Their FDA was granted 510 clearance for quote, Alzheimer's diagnosis.

Sorry, Alzheimer's dementia diagnosis software. FDA granted 510 clearance for this company's Alzheimer's dementia,

Alzheimer's and dementia diagnosis software.

I don't know about you edien, but to me that sounds like wonderful news. I mean we all know that, that, that Alzheimer's and dementia, I mean personally, you know I have very close people in my family that are very impacted by these diseases.

So gee, that sounds wonderful.

Well let's take this a step further.

So let's go to FDA's website and let's take a look at their 510 summary and let's look at their high level labeling specifically for their indications to for use to see exactly what this device is was cleared for.

Now there's a lot of words in this,

but here it is, the Eros.

I'm sorry, it's got to look at the bigger version here. Oh, it's the same thing. I'm sorry, the arrow score. That's the ERA score. Sorry. Is intended for automatic labeling,

visualization and volumetric specifications of segmented brain structures from a set of MRI images.

The software is intended to automate the.

Sorry. It's just a little bit difficult to read here,

automate the current procedure for identifying, labeling and quantifying the volume of segmentable brain structures identified on the Mr. Images. There's bottom line, Eddie, and there's a lot of words in there.

However,

is Alzheimer's or dementia or anything like it either mentioned directly or indirectly in their high level labeling?

Absolutely not.

Now, to me,

and I'm one of the more aggressive regulatory professionals around, but to me,

that's a bit of a reach to say that our device was granted clearance to diagnose Alzheimer's and Parkinson's in a press release when in fact, you look at what it was actually cleared for where Alzheimer's and dementia are not even mentioned.

Now, to be fair, I'm only looking in the high level labeling. I am not looking in the low level labeling. It could be very well that the company did mention it in their low level labeling, like in their directions for use or their device description or something like that.

I don't know, but I'm just making the point that it's not in their high level labeling. So do you think that that. And I'm going to use this pun intentionally, Eden, do you think that the company saying that our device can be was granted clearance for Alzheimer's and dementia diagnosis?

Is that substantially equivalent to the gobbledygook that I read in their indications for use?

Etienne Nichols: Well, I would need to look close. Honestly, the way I look at it, the attended use being a broader umbrella and those Alzheimer's and specific dementias being more specific intended indications for use.

I don't know if there's some latitude there. I guess I would need to look again at what the intended use that you just read.

Mike Drues: Fair enough. Fair enough.

And the last thing that I'll mention, because I know we got to wrap this up, is this is not just a concern for the FDA from a regulatory perspective, it's a huge concern from a product liability perspective.

And imagine that this software doesn't diagnose Alzheimer's in a particular patient and they go on to experience harm and the company gets sued and I guarantee they will get Sued.

Imagine what a decent expert witness like myself can do.

Well, you're advertising this product as a diagnosis for Alzheimer's and dementia, and yet nowhere in your high level labeling is it indicated for that.

It doesn't take a JD from Harvard or Hopkins to appreciate Ka Ching. Ka ching, Ka chic.

Okay,

let's go ahead and wrap this up.

Etienne Nichols: Yeah, yeah. The only thing I'd say about that is that's, that's expected, that's dependent on them lying about the product and it actually not working. If it does work,

and just the fact that it's not in the intended use, I think you still have the ability. I mean, don't get me wrong, off label use is a big deal,

but so is the first amendment.

Mike Drues: And no, you're right. Fair point. And if in fact it can do these things, if in fact it can legitimately diagnose Alzheimer's and dementia and so on, which is wonderful, obviously great, then they should go to the FDA with the evidence to support that claim, prove that claim, and then add it to the label.

Etienne Nichols: Yeah, yeah,

no, that's a great point. Okay,

that was a good example.

You got me curious. Now I have to dive a little bit deeper there. But what else, what are the thoughts do you have on all of those?

Mike Drues: Well, just to kind of wrap this up, because I know we need to end here and there's still so much more we could talk about, but just a few things to keep in mind.

First of all, as I said before with my friends at the fda, but also people that do webinars and podcasts,

don't be afraid to use specific examples, don't be afraid to mention specific devices or specific companies. As long as this is based on publicly available information.

FDA says you can get a warning letter for this. Well, warning letters are publicly available most of the time. Time pull up the warning letter and say, here's what the warning letter said.

You know, why do we, you know, get, get hypersensitive about that? After all, you know, I used to teach in medical school.

We taught in medical school that way all the time. We would say that when doing this particular surgery, Dr. Smith did it that way and Dr. Jones did it that way.

We didn't say that one doctor did it one way and another doctor did it some other way.

More importantly, beyond that, being a medical device professional know means a lot of things, but one of the things that it means is individual accountability.

I don't care if you're in a, in a company or at the FDA or maybe somewhere else you should be accountable for what you do and for what you say and similarly for what you do, don't do and what you don't say in policies like, well, we don't want you to mention names in meeting notes.

I just think that defeats that purpose.

More importantly, in terms of the content of today's discussion and Ian, and you feel free to add anything from this, this list or to this list if you want. Just a couple of things to reiterate,

learn from other manufacturers, misfortunes or mistakes. There are certainly many of them to learn from. This was one of the tenants of the CAPA vs PACA webinar that I did a few weeks ago.

Corrective action, preventative action versus a preventative action, corrective action.

I think that we should be more proactive in fixing problems rather than reactive.

Consider obviously what FDA says or recommends in regulation and guidance, even in presentations like the one that we were sort of reviewing today.

However,

don't take what FDA says or recommends as gospel. It's coming from God. And I apologize, to use a religious metaphor, I don't mean to be offensive.

We should always ask questions.

And one of the most important jobs of a good regulatory profession professional,

not an average regulatory professional, but a good regulatory professional, is to ask questions, especially the questions that are not so easy to answer or the questions that other people don't really want to ask.

I find it unfortunate, Eddie, in that in this society today, it's become sort of not politically correct to ask questions sometimes. And quite frankly, I think that's dangerous. Those are just a few thoughts I can go on and on, but anything you would add, edien, and then we can wrap up this yourself.

Etienne Nichols: No, this is, this is good. I definitely agree that we need to be more proactive and I like that.

I like the idea of being a little bit more lateral to take examples from the drug world, take examples from even, you know, the food world. It's just there. There are kind of like rings, I guess.

I see. We, we focus on medical device. You go one ring out, you have the drug,

food, tobacco, et cetera industry. Then you have a little bit further out other regulated industries, aerospace, et cetera. And there's lots of examples we could learn from all of this.

Those. So it's good.

Mike Drues: Maybe that might be a topic of a, of a future podcast as we can compare and contrast devices for drugs and biologics. And, and I love your inclusion of foods in there.

Etienne Nichols: Yeah, yeah.

Mike Drues: There are some important regulatory differences.

Etienne Nichols: Yeah.

All right. Thank you so much. Really appreciate it. Those who've been listening. Thank you so much for listening to the Global Medical Device Podcast. Leave us a review. Reach out to Mike or myself on LinkedIn.

We'll put our emails in as well so you can reach out. But but until next time, everybody take care.

Thanks for tuning in to the Global Medical Device Podcast. If you found value in today's conversation, please take a moment to rate, review and subscribe on your favorite podcast platform.

If you've got thoughts or questions, we'd love to hear from you. Email us at podcastreenlight Guru Stay Connected for more insights into the future of medtech innovation. And if you're ready to take your product development to the next level,

Visit us at www.greenlight.guru. until next time, keep innovating and improving the quality of.