What are the 4 buckets of information that MedTech professionals should consider when commercializing their device? Where is the line between perspectives when it comes to regulatory affairs professionals and regulatory affairs attorneys? Those are just a few of the items covered in today’s live discussion with Mark DuVal.
Mark is the founder and president of Duval & Associates. He’s been in healthcare marketing and advertising for over 20 years and is a leading expert in medical device promotion. In today’s episode, you’ll learn his tips for creating “appropriately aggressive, yet compliant” ad campaigns. Learn from Mark’s expertise as he discusses the four buckets of knowledge for information sharing, the different perspectives between regulatory and legal, and how to think about the information provided with a medical device.
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Some of the highlights of this episode include:
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The difference in perspectives between a regulatory affairs professional and a regulatory affairs attorney
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Best recommendations for regulatory affairs professionals when approaching off-label
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Examples of when the dissemination or communication of on and off-label information comes into play
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General and specific use, and being specific with your indication for use
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Whether a case study could be built around a physician’s off-label use
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How compliance monitors sales for off-label promotion
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Ad promo enforcement action
Links:
Cardiac Arrest: 5 Years as a CEO on the Feds Hit List (book)
Washington legal foundation case
General/Specific Intended Use - Guidance for Industry
Memorable quotes from Mark DuVal:
“The regulatory affairs professionals are, a lot of times, they’re biomedical engineers and scientists, and they are much more steeped in the medicine and the science as we would be as lawyers.”
“It’s kind of a mantra I make everyone repeat when I do a training exercise – I make them repeat after me, truthful, not misleading, fairly balanced.”
“You have every right to participate in social media. But again, you’re still regulated.”
“We don’t feel people should unnecessarily leave money on the table, nor should they foolishly aggravate FDA and receive a warning letter and get told to cease and desist.”
“When you’re in the trenches day-to-day, trying to convince them to use something that’s real-world data is work. It can be done, though!”
Transcript:
Etienne Nichols
00:00:51.050 - 00:00:52.850
Hey guys, welcome back to the podcast. My name is Etienne Nichols and I'm the host of today's episode.
This is in today's episode I got to speak with Mark DuVal and I spoke on the topic of ad promo and the difference in regulatory affairs and legal perspectives.
Before I get into some of the things that we talk about, I want to give you a little bit of context about this episode because it's a little bit different. This episode was recorded virtually, but it was recorded in front of a live audience.
So, if you see some of us during the discussion talking about the comments section or some of the things people are asking or the questions, that's what that's about.
Just full disclosure as you're driving your car or listening to this episode, that's what happened there. Also, at the end of the episode, we opened it up for 30 minutes of question and answers from the audience.
Now, that is not included in this episode or in this recording that is being published. So, you won't have access to that. If you're interested in listening to that Q and A, let me know.
We were planning to put that in the community just as a separate section, just so that you wouldn't have to be bothered bogged down with those question and answers. It's very good stuff but let me know if you're interested in hearing more about that. Okay. We covered a lot of ground.
We talked about just a couple different things that came to my mind are things like what are the four buckets of knowledge from information sharing? This is a fantastic framework that Mark throws out there. He doesn't just throw it out there.
He goes into very much detail about each one of these different buckets and it's fantastic knowledge that he shares. Also, what's the difference in perspectives to consider when utilizing a regulatory consultant for versus a legal advisor?
They have two different perspectives. They're looking at it from Two different directions. Both are very important, and we talk a little bit about that also.
How should we think about the information that we provide with our medical device during the sales and marketing of medical devices, it's very important. Sometimes things that medical device manufacturers don't think enough about. We covered so much ground. Mark DuVal is fantastic.
He's the founder and president of DuVal and Associates. He has over 20 years of experience in healthcare marketing and in advertising.
He's a leading expert in medical device promotion, an attorney, and with so much experience. I first heard him speak at raps, where he is a fellow. He's a fellow at raps. I heard him speak in Phoenix, Arizona.
I was very much impressed with his insights, his strategies, his ability to break down complex topics in a way that is easy to understand, to create a successful ad campaign that complies with regulatory guidelines and effectively communicates the value of medical devices to target audiences.
So, this episode is chock full of his expertise, his practical tips for creating what he calls an appropriately aggressive and effective, yet compliant ad campaign. So don't miss this chance to hear from one of our industry's top thought leaders.
I hope you enjoy this episode with Mark DuVal on ad promo and the legal perspective in medical device development.
Etienne Nichols
00:03:46.460 - 00:03:47.100
Hey, Mark.
Mark DuVal
00:03:47.660 - 00:03:48.140
Yes.
Etienne Nichols
00:03:48.540 - 00:03:49.180
All right.
Mark DuVal
00:03:49.940 - 00:03:50.420
This is great.
Etienne Nichols
00:03:50.420 - 00:04:03.300
We should be live at this point. I'm just gonna see if there's anybody out there if you want to put something in the chat just to let us know you can hear us.
We'll get going in just a few minutes here. All right. Hey, Joe, how are you doing?
Mark DuVal
00:04:03.620 - 00:04:04.020
Great.
Etienne Nichols
00:04:04.100 - 00:04:09.380
Okay, good. We have some people. And we also found the chat curious where everybody's coming in from.
Mark DuVal
00:04:09.460 - 00:04:09.820
If.
Etienne Nichols
00:04:09.820 - 00:04:15.500
If you care to share. I personally, I'm from in. I'm in Nashville right now. I know. Mark, are you.
Mark DuVal
00:04:15.500 - 00:04:15.680
You.
Etienne Nichols
00:04:15.750 - 00:04:16.950
You're in Minneapolis right now, aren't you?
Mark DuVal
00:04:16.950 - 00:04:23.030
In Minneapolis? Downtown Minneapolis, 18th floor of the Medical Arts Building, right off Nicollet Mall.
Etienne Nichols
00:04:23.270 - 00:04:40.070
All right, looks like we got some people from San Diego. Chris is from. Okay. Linda's from Minneapolis. I saw someone from Nashville. I have to.
Let's get together sometime, guys, but let's go ahead and get started. So just to let everybody know, we've got about 90 minutes scheduled, if that. Is that still okay with you, Mark?
Mark DuVal
00:04:40.630 - 00:04:41.190
Yep.
Etienne Nichols
00:04:41.360 - 00:05:02.960
Okay, so we're just playing about an hour for the conversation. If you have questions, those of you in the audience, feel free to put those in the Q and A.
But the way we're doing this, we're just going to kind of treat this Like a podcast that. That is the intent. The general conversation will be recorded and released on our RSS feed as a podcast.
And then the last part, the Q and A that might be.
Mark DuVal
00:05:03.120 - 00:05:03.480
We.
Etienne Nichols
00:05:03.480 - 00:05:53.310
We haven't decided exactly how we're going to release that, but feel free to ask your questions throughout and we'll definitely try to get those towards the end as well. And yeah, excited about the topic. All right. Welcome to the Global Medical Device Podcast. So, my name is Etienne Nichols.
I'm going to be the host of today's show. Today with us is Mark DuVal, the founder, president and CEO of DuVal & Associates.
He has over 20 years of experience in healthcare marketing and advertising. He's a leading expert in medical device promotion. I first met Mark at the RAPS conference back in September.
Side note, he is a fellow at raps, the Regulatory Affairs Professional Society. So, his pre. His presentation on ad promo there was outstanding. I was really excited to hear that.
And so personally, I've been waiting months for the opportunity to have another conversation with Mark. So, Mark, I'm so glad to have you on the show today.
Mark DuVal
00:05:54.430 - 00:05:59.950
I'm glad to be here and it was fun meeting you in Phoenix and it'll be fun doing this follow on podcast.
Etienne Nichols
00:06:00.670 - 00:06:15.140
So, the topic that we have today is ad promo. Just. That's the short version, I guess.
But before we get into the nitty gritty of that, we usually talk about quality or regulatory topics, but this is, this is a marketing topic, but it is quality and regulatory.
Etienne Nichols
00:06:15.540 - 00:06:16.980
So maybe we could start out by.
Etienne Nichols
00:06:16.980 - 00:06:24.020
Talking about what ad promo is to Medtech and maybe why MedTech professionals should even be concerned with this.
Mark DuVal
00:06:25.460 - 00:09:56.770
Yeah, well, foundationally, you know, once you get a device clean, you know, the whole regulatory strategy that you have in order to get a device cleared or the grant of a de novo or approved as a PMA is to have a baseline representation claims that you can make about the device.
And that you have to think that through very carefully because the more sophisticated your claims get, the higher up the regulatory pathway you have to go.
And our job is, you know, when we get involved with the company very early on and help put together a submission or do the submission for them, is trying to get, you know, start with the end in mind, what is it you'd like to say this product does?
And then we benchmark that against the competition, whether it be a predicate for a 510(k) or just another product out there that the novo is close to or a PMA is close to, and have you identify what Is it you want that product to see that makes you differentiable in the marketplace. And then we work with you to do sort of a regulatory assessment to say well look, if you now if you want to, there's a scale.
If you want to make it a very, a fairly pedestrian claim, inherit the underlying, basically the underlying IFU from another product on the market today, the intended use statement, then we'll take you down the 510 path.
And the more extravagant that claim gets or the more detailed that claim gets, the more it migrates from a tool to being a treatment, for example, the more likely you're going to challenge yourself to the edge of the 510 program may end up on as being a de novo, still a Class 2 moderate risk device, but for which there's no predicate.
And now you've inherited instead of substantial equivalence as the standard for getting your product through, you're going to inherit the PMA standard of reasonable assurance of safety and effectiveness. But with a de novo it's kind of like a PMA light in terms of the expectations for the quantum and the quality of the data you need to submit.
So we're always, that's it's very, it's really critical for the, the company first to know what it wants to say about its product and then when it gets that clearance or that grant to de novo or that approval, then it comes in the, you know, the, the magic of what the marketers would like to say beyond that to extrapolate from that, that baseline intended use statement to what else can we say?
And by the way, if we develop additional data going forward, what can we add to the promotional platform without upsetting FDA or violating the principle that we're outside the scope of our intended use statement that was granted by FDA.
So, and from a quality perspective, we always tell people frankly that we don't like the promotional review process to be in the quality system, although it is a quality to follow the claims matrices to make sure you're staying have fidelity to the claims that you're allowed to make you.
It is a quality like system, but I never like ceding to FDA the authority under the quality management system the right or the ability to look at promotional materials. Now they'll assert that. Yeah, they'll assert that all the time and companies do it all the time.
So don't get me wrong, but we sometimes talk companies into having a separate promotional after promotional review process that's like their quality system check if you will.
But it's not within the core quality system itself because I never like to give the jurisdiction authority over advertising promotion to the FDA that easily.
Etienne Nichols
00:09:57.170 - 00:10:27.370
Yeah, that's interesting.
So, and before we go too far down, I, you and I were talking a little bit before we had this conversation about the difference and maybe what a regulatory affairs professional, their scope and really perspective might be the word versus a regulatory affairs attorney. And, and the legal side. What, what are the differences in those perspectives?
Because I think you've already kind of touched on it as far as, you know, whether you, where you house some of these documents. But what, how would you describe the differences in those perspectives?
Mark DuVal
00:10:27.370 - 00:13:02.020
That's a great question. And I, and I, I don't say this by way of offending anybody because there's no right or wrong.
The regulatory affairs professionals are, you know, a lot of times they're biomedical engineers and scientists and they are much more steeped in the medicine and the science than we would be as lawyers. Although I've learned a lot through a 36-year period just through osmosis from some very smart biomedical engineers and scientists and physicians.
But we tend to look at the, we're not, so we're not very deferential to the agency. We know that the agency often exceeds its authority, its jurisdiction authority.
So, when you even look at advertising promotion, they're often offending the First Amendment. They've lost a lot of cases that have kind of forced FDA to reshape or rethink how they regulate advertising promotion.
But the general difference between I think a regulatory affairs professional and a lawyer is, and I'll talk about this in the context of maybe the 510 program, when a regulatory affairs professional puts together a 510, they, you know, it's an evidentiary document. They're thinking very hard about all the evidence that they need to put in the framework that's given to them in the eSTAR program or E Copy program.
And they want to put it together kind of as FDA directs them to. And we don't think of just as an evidentiary document because there's a story to be told.
We think it as an advocacy document owing to our lineage as lawyers. It's an advocacy document with evidence. So that's how we look at it.
And we're just trying sometimes to help the regulatory affairs professional to say, don't just immediately assume that FDA's request for information or their perspective, for example, on the definitional elements of the 510 program, i.e.
that you have the same intended use, that you have the same technological characteristics, or if you have different technological characteristics that you truly are raising different questions of safety and effectiveness. You can push back and fight that. And that's what our job is. And we do that all the time.
And one other thing the FDA will always do is they'll start talking about, well, you need to establish in a 510 the clinical benefit or utility for that device. And the immediate visceral reaction I have as a lawyer is time out. No, we don't, we don't have to.
As a 510, when we choose a predicate, we inherit the underlying regulatory presumption that the product is as safe enough, the predicate families, establish the essential utility of the product predicate family, and it's generally safe and effective. I just have to show I'm as safe and effective as that predicate that I've chosen.
Etienne Nichols
00:13:02.100 - 00:13:14.140
So, can you give an example? Yeah, give me an example of them change maybe going further or asking for something when based on the predicate.
What are your, what are your examples?
Mark DuVal
00:13:14.140 - 00:15:20.760
Well, for. Here's another idea.
So, there's a, there's a section of statute that came out under, during the least burdensome years when the least burdensome statute was being enacted. And it was. And then there were amendments. The FDA came out. There was a statute that industry asked for. And it's called, it's 513i1e of the statute.
And I just, I roll that off because I deal with it so often on appeals. But under 513i1e, the FDA is not allowed to assume a use for the product.
So, let's say you take a fairly modest pedestrian intended use statement and you just want to breeze through the 510 program and get on the market.
And maybe in the future you have some idea for some other uses to which the device would be put and for which you will go back to the FDA in sort of a staged approach, right, to get additional claims. Well, sometimes in that initial submission, FDA will assume that you are going to claim uses that you're not yet claiming or you hadn't submitted.
And when they assume that inflated use, which might be a treatment claim, for example, versus a tool claim, they'll then conjure up data requirements that meet that assumed use and are much higher than what you would do normally for the 510 claim you're seeking. So, when they do that, they're violating the statute. They cannot assume an unstated use.
Now, if they really believe that the product, product might be used there, they literally under the statute, have to go to Dr. Sheeran the center director for a finding that there's a reasonable likelihood that harm could result from this assumed use.
And they can then make you add limitations of use to the labeling, but they can't preclude your clearance for that more pedestrian claim you're seeking. So that's just one example of many that we confront or face when we're working.
When a company comes into us, they won't even see or identify these issues. And we'll go, yeah, here's an issue and you know, we need to attack it. And then we work a lot on least burdensome stuff as well.
When the FDA asks for more data than that to which they're entitled.
Etienne Nichols
00:15:21.000 - 00:15:31.880
Yeah, that makes sense. So, if we take this back to add promo then, for medical devices. I've heard you talk about four buckets of information.
I wonder if you could expound on those four, four buckets of information flow.
Mark DuVal
00:15:32.200 - 00:18:55.540
Yeah, that's a great question. And I'm gonna, I'm gonna cheat by looking at some of my own slides as I do that. All right, the first.
So, I've taught this for years and actually we wrote a chapter for a book. A lawyer is a good friend of mine from Epstein Becker out in Philadelphia.
And we were asked for Food Drug Law Institute to come with a up with an analytical framework that would help marketers and regulatory affairs professionals understand how we communicate information broadly about a device or a drug, in that case to the marketplace. And I, I thought of it as I, I created these four buckets of information flow.
And when I teach courses on this, whether it be at convergence for wraps or it be for a client, we talk about the promotion of on label information because of course, fundamentally we're, we can only lawfully promote on label. Although. Hold that thought, I'll come back to that in a minute. Secondly, we talk about the dissemination of off label information. And that's.
That was created back in the late 90s, early 2000s, where the FDA lost a major lawsuit or major case in the Washington Legal foundation, which allowed us to engage in the exchange of medical and scientific information. So that's because it's first amendment protected. FDA was never.
A government agency is never allowed to act as a filter of what information is being exchanged in society, whether it be from a manufacturer to a consumer, you know, a patient or a manufacturer to a physician, or from a physician to a patient. They just aren't supposed to be involved. But what they can regulate is to ensure that what is being discussed is truthful and not misleading.
So, when you disseminate information about off label uses of your product. You can do that, and FDA has two guidance documents that allow you to do that.
One is on a reactive basis where somebody unsolicited asks a doctor, asks the company a question and then the first amendment door is opened, and you can respond to that with information that's tailored to the question that was requested.
There's a second guidance document that addresses proactive dissemination and that allows you to proactively send information out the door, usually from your medical affairs group, smaller companies that might be regulatory fairs or clinical or whatever, but you can send out affirmatively or proactively off label information about your product. So that's bucket number two, dissemination. Bucket number three is communication. That is a huge bucket, and I can't take the time.
But it's informally safe harbored ways. You might be able to discuss off label uses with folks out in the medical, medical community. And we cover under that bucket, which is huge.
We cover press releases and social media and grants for physician-initiated trials and off label uses or grants for CME discussing off label uses.
Or maybe when you retain consultants under the auspices of a consulting arrangement, can you impart information about potential off label uses in order to extract information about, you know, what the clinical study might look like, what the messaging, marketing messaging might have to look like, etc. So that's a, that's a very big bucket and we usually whiteboard with companies all the time on that one.
Etienne Nichols
00:18:55.540 - 00:19:01.700
Takes a lot of time and time out. So, when you say safe harbor, what I'm not super familiar with that term, what does that mean?
Mark DuVal
00:19:01.700 - 00:21:02.210
Well, that's a really good question. That is actually my construction. It's a figment of my regulatory imagination. In this case. There are safe harbors under the anti-kickback statute.
I'm not going to get into that. But these safe harbors, these what I call informally safe harbor activities, are things that the FDA recognizes. Let me give you an example.
When you do a press release about an off label use, maybe you've got a cleared or approved product and it's on the market and now you're studying that product for another use and you want to do a press release talking about the enrollment of the first patient, or talking about the enrollment of the last patient, or talking about the results that have come out. The FDA tolerates in a press release the discussion of an off-label use because it's an informally safe harbor activity.
They know under rule FD, for example of the Securities and Exchange Commission, publicly traded companies have a requirement to Talk about information that might be material to an investing public. So, they allow you to talk about futuristic uses of an already approved product. They would otherwise be considered off label promotion.
And even when it's a privately invested company, it's not publicly traded.
The FDA seems to extend that rationale that you need to talk to your investors and to the public generally about what your, what your company is doing and what it's up to. So that's an example of an informally safe harbor.
The other one would be when you do a consultancy, if you signed up somebody under a confidentiality agreement, a consulting arrangement, and they're sharing information with you and you're sharing information that hey, we're going to pursue this off label use or this new use, which is today off label.
But we want to get some information from you about what you think about how we might market that if our clinical trials come out appropriately, we get on the get approved, we get on the market. And so, you're engaging in off label discussion before that product is actually approved for that use.
But that's an informally safe harbor activity at that point.
Etienne Nichols
00:21:02.450 - 00:21:16.050
Okay, that makes sense.
So, we have promotion of on label information, dissemination of off label medical scientific information, communication of on and off label information. I might ask for some examples of those. But what was the fourth bucket?
Mark DuVal
00:21:16.370 - 00:23:39.980
Yeah, the fourth bucket is kind of, it's, it's relatively new. It really, it's not super new. It came from 2000.
Well, it's been developing for a while, but it really solidified in 2016 with the Howard Root Vascular Solutions case, which is a very famous medical device case.
But there's been a series of cases that the FDA has had to fight in court where both pharmaceutical and medical device companies have basically said you're overregulating free speech. And you know, so when you think about if you're disseminating off label information, what makes that lawful?
It's because if you're truthful and not misleading, if you have disclosure disclaimers and disclosures about the information you're about to share through dissemination, that's what remedies the fact that if you put that, if you actually promoted for that use, the FDA would consider it adulterated, misbranded, send you a warning letter, probably tell you to cease and desist. Right.
If you extend that thinking of dissemination to off label promotion, you're asking yourself, if I can disseminate that information, why couldn't I promote it in the same fashion with appropriate disclosures and disclaimers which make that otherwise off label information actionable? By the FDA on an enforcement basis.
And it came about because, for example, in the Hard Root Vascular Solutions case was a really important case where the CEO and the company were basically criminally charged and civilly charged with having violated the false claims act and then. And by way of using the mail wire fraud, and that made it criminal. And Howard Root is a very brave CEO, and I know we're gonna.
You're gonna have him on in the future, but he. They spent $25 million in five years of his. Of their lives.
And I know the chairman of the board of that company at the time, and the board was behind it because they felt that somebody had to sort of get FDA under control. They were prosecuting Howard for allowing the organization, which he did not do anyway, for allegedly promoting an off-label use for the product.
And for that, as a CEO, he was strictly liable. He is responsible. And they fought that in court.
Etienne Nichols
00:23:41.900 - 00:23:48.260
So, for the CEO to be strictly liable and responsible, what does that mean? Like what, what's the potential implications there?
Mark DuVal
00:23:48.260 - 00:27:09.500
Well, there's a, there's a group, there's a couple of cases, the Dotterweich and the park doctrine cases that are where we refer to as lawyers, where the FDA years ago established the fact that under the Food, Drug and Cosmetic act, if you as a responsible executive allow criminal behavior to go on, but underneath your nose, you are personally responsible for it.
So, if a sales rep in the case of Howard Root was arguably promoting for an off-label use of the, of their device, then Howard Root as CEO is responsible for it. And see, he didn't ever. He actually did the promotional programs because Howard is a lawyer by training.
So, when he would train the reps, he would tell them, you can't sell for this particular use in the perforator vein for the, for the product is a very small little vessel. The product was used to ablate for varicose veins, basically.
And the FDA had this idea in their heads, given the broad intended use statement that they were granted, that this little connecting perforator vein between the two major veins was off label. And it didn't make any sense at all.
And it was funny because on cross examination, FDA's branch chief, the Howard Roots defense lawyer, essentially got the branch chief to admit it could be unlabeled. So, the case was done, but it took five years to get there.
And can you imagine how much you'd sweat and worry and how much Howard's wife worried for his future, their future. But he was a very brave guy and just felt that he stood on principle. And he won. That's the fourth bucket. That's our fourth bucket. You can.
There is an argument to be made that if you do it carefully and appropriately, you can do that. And let me add one more thing at the end before I tell that.
The reason I'm getting more confident in that position is that FDA in June 2018 put out a pretty good guidance document called Medical Products Communications that are consistent with FDA required labeling. And they're in. That guidance document essentially enunciated the First Amendment standard.
And I was like, excited because like FDA, you're finally like getting there. You finally got it. And it's a good, it's a good guidance doc. Now it doesn't, it's not broadly permitting you to promote off label. But here's the.
Let me share one last thing. Here's how the courts look at it. FDA says we don't care if the speech is truthful, the promotional speech is truthful.
If under our jurisdiction authority, it's adulterated and misbranded, you didn't come to us for clearance or approval, then you've engaged in criminal behavior. You're promoting, illegally promoting off label. And the courts sort of switch that around. They say, you got that wrong, FDA.
Your statute sprung from something called the Constitution, which is pretty much bedrock for the country. The Constitution gives us the First Amendment.
And if the speech was truthful and not misleading, then you cannot use truthful speech, you cannot prosecute truthful speech. And that's the tension.
And once FDA finally figured out the courts were immovable on that concept, they started moving and they got more permissive in this arena.
Etienne Nichols
00:27:09.580 - 00:27:38.280
I see. Interesting. And so, I'm going to take a quick moment, real quick, because you've mentioned a lot of things. One was the book that you helped co-write.
So, I'm bringing this up to say in the show notes, those of you listening, if you're interested in hearing more about this, we'll put links to the guidance documents of off label dissemination for reactive or proactive, as well as the Medical Products Communications guidance document and Cardiac Arrest. Howard Reed's book, I have it on my desk right now, working through it. It's a great book, highly recommended.
Mark DuVal
00:27:38.280 - 00:27:38.560
Yes.
Etienne Nichols
00:27:38.560 - 00:28:22.250
He is going to be on the podcast before too long. So, I'm excited about that. So, okay, so these are from a medical device professional perspective, I typically think. Okay.
But I, I really have to be careful with what I say.
But you're what, what you're saying, it almost flies in the face of what I've always heard about any kind of communication about these different, these different aspects. So, you have a good relationship both with the agency and with the industry.
I'm curious, what are the best recommendations for regulatory affairs professional when they're, when they're approaching these subjects. Obviously, we don't want to just assume that we can promote off label. You know, we have to be careful. But.
But what, what, what's the advice and recommendation you have about that?
Mark DuVal
00:28:22.890 - 00:29:27.990
That's funny. I just got off the phone late last night with an Australian company talking about this.
The natural tendency or proclivity of a regulatory affairs professional again is to be fairly deferential to the agency and, and they should, we all should there. I have great relationship here. I really love working with the agency. I respect them greatly.
But my job is to challenge and I'll tell you what, by way of an example, years ago when I was general counsel of 3M's pharmaceutical business, I was asked by the executive committee of the law section of Pharma, the big trade association for the pharmaceutical industry to debate a woman named Ann Witt who was a jd, a lawyer who was head of the division for drug marketing Advertising Communications. It's now called Office of Prescription Drug Products.
But the reason I was asked to debate them is because FDA at that point was taking the stance that the industry could not do. Listen to what I'm about to say. The industry could not do direct to consumer advertising. Now I'm going to look you in the eye at the end.
I'm going to ask you how many TV ads for drugs have you seen in your life?
Etienne Nichols
00:29:28.550 - 00:29:29.510
Could even say.
Mark DuVal
00:29:29.750 - 00:30:57.110
But that shows you how the agency has morphed over the years. They actually, they didn't want you to disseminate off label information. They didn't want you to engage in direct-to-consumer advertising.
And frankly it was the Federal Trade Commission who I remember assigning employee employees to the FDA to help them, nurture them to come along to accept the idea. You got to allow people, companies to the patients want it. You got to allow companies to advertise.
Now there needs to be in a format that we have to agree upon. And that's why you see all of those, you know, the benefit, both the benefits and the risks are juxtaposed in the course of the ad.
Some of it will scare, some of the risks will scare you to death. And then they've had to trend, then they've had to transition that to social media where you might be character limited to 100.
You used to be 144 characters. Now it's 300 some whatever.
And how do you get the fair balance of risks and benefits, the you know, indications, the contraindications, the side effects, the precautions, the warnings, etc.
FDA has morphed in an amazing fashion over that time, and they did a much better job with social media once, once the, the dam was broken, if you will, direct to consumer and they accepted that they would were going to have to do that and they issued guidance on how it could be done. Then they segued into social media a lot more readily and did a pretty good job of it frankly.
Etienne Nichols
00:30:59.030 - 00:31:15.110
That makes sense. So, you mentioned the fair balance part.
So, and I just want to kind of circle back to that because you mentioned a couple times truthful, not misleading, fairly balanced, but the fairly balanced. So, what if you could expound even a little bit more on that or maybe any of those that might have any kind of subjectivity to the term.
Mark DuVal
00:31:15.580 - 00:32:40.230
Absolutely. So always keep in the backdrop.
I always, it's kind of a mantra I make everybody repeat when I'm, when I do a training exercise, I make them repeat after me, truthful, not misleading. Fairly balanced seems simple. And all of the Food, Drug and cosmetic act, advertising promotion hangs on that general's general principles.
We all, I think, kind of know what truthful and not misleading is and government regulates that whether it's a consumer product or a drug or a device. But when you get to the point of fair balance, it just means the FDA.
I give away an example when I train, when I used to train, talk to review promotional materials for marketers. They'll have, they might have back in the days when we had a lot of sales collateral material and they had a six-page piece, right.
And you open it all up, they'd have all the benefits on the first five pages, and you knew it was on the backside, right. Or maybe on the inside cover of the back because they didn't want to be on the back because that was easily seen.
All, you know, the risks in small print at the bottom of the page and after you say wait a minute, wait a minute, we want fair balance, we want you to juxtapose this benefit with this risk, this benefit with this risk and so on and so forth all the way through the piece and making sure it's readable and it's legible and you know, make a fair attempt. Again, it's all about context. It's all.
And that's part of being truthful, not misleading is you want to leave a fair impression about what the product is and does and what it is not and does not do.
Etienne Nichols
00:32:41.030 - 00:33:03.550
So, with, with social media though, there's a lot of times, I mean, you mentioned the character limits, but there are other ways to interact on social media with emojis or thumbs up and things like that is, I don't want to go too far down that rabbit trail necessarily, unless you want to. But how does, how does the agency look at that?
What are, what are the people who could be held liable in those cases when they're, they're interacting on social media?
Mark DuVal
00:33:03.550 - 00:34:24.790
Yeah, that's a great, that's a great.
Social media has been very good and a difficult thing for people like me at the same time because how do you help people navigate, you know, Instagram and TikTok and Facebook and whatnot.
And yeah, there's, in Twitter has had a, there's been a number of promotional warning letters where the thumbs up has gotten people, you know, companies in trouble because there'll be the discussion that ensues online in social media and then they'll, they'll, you know, the marketer from a company or a sales rep just cannot contain themselves. And they say, well, I'm on my private time, I'm on social media now and I'm going to defend my product.
And if I like a, if I hear about an off-label claim being made about my product and how safe it is, I'm going to put my thumbs up.
You know, and FDA has actually issued warning letters for companies’ kind of setting up that venue or participating in a venue they didn't set up but being effusive about commenting on or putting thumbs up, agreeing with off label uses and things.
The company, if you're going to, you have every right to participate in social media, but again you're, you're still regulated and your employees are still regulated because they're representing you, the company. So, you have to be careful about how you participate in social media.
And it, there's a lot of nuances to that and I won't drill down on that right now unless you ask me a question that forces me to do it.
Etienne Nichols
00:34:25.040 - 00:34:46.240
Okay. And maybe, maybe that question will come up. I don't know. We'll see.
But if we go back to that four bucket of information flow because I really love that framework, I still think so, the dissemination of off label medical use or the communication of on and off label information. Can you give some examples of when that might come into play? Or just how could you expound on that?
Mark DuVal
00:34:46.640 - 00:34:51.280
Yeah, let me. And I'm going to actually get myself down to that slide for my own benefit because it'll help me.
Etienne Nichols
00:34:51.860 - 00:34:52.180
Yeah.
Mark DuVal
00:34:52.500 - 00:38:09.450
Know what I'm talking about. But because I do put actually a lot of things in there. I don't, I might not even have it. Yeah, I have it right here.
So, dissemination, you know, is a really helpful exercise. It's kind of obtuse indirect marketing, but you have every right to do it.
So, if, if there's a peer reviewed journal article that comes out on, on a use of your product, on an off-label use, you can, you can exchange that. And FDA has, like I said, these two guidance documents. One of them allows for the proactive dissemination, which I really like.
And so, when the Washington Legal foundation case first came out, Judge Lamberth kind of set the stage for what he thought dissemination should look like. And I remember FDA, actually I, because I used to teach a.
For about five years, I taught with a woman named Deb Wolf from FDA and Promotional Advertising Policy Group for CDRH.
And I remember one time Deb coming me say, hey, you know the, the FADAMA, which is a statute they'll love for off label dissemination, was sunsetting and we've got this WLF case and I was told to ask you what, what do you, what would you think we should do? And I just, my, you know, I'm an n of 1 in terms of input. Right.
But they asked me, so I, I said I would, I would, I would take the Washington Legal Foundation case, and I would basically memorialize it into a guidance document. It's pretty good, covers a lot of great ground and I think it's a great starting place for us as an industry. And the FDA did that.
And it is pretty good. It's a little even over broad from a constitutional scholar standpoint, but it's livable, it's doable.
So, what happens is if you want, basically if you want to disseminate information, you have to, you have to, you can mail out like we used to do it at 3m. The very first time the WLF case came out, we took a, basically a folder.
And at the top of the folder, it had the name of the publication or the article and the authors and the publication where it was published. At the bottom it said 3M Pharmaceuticals. You open it up in these two sleeves and on one sleeve you have a letter from the medical.
The assistant medical director said, hey, this is an off-label use of this product. And the on-label uses are in the package insert stapled to this letter. And you could get the package insert for that product.
And then the right side, we had a bibliography of articles that were pro, con or indifferent about the use of this device in that off label use to be fairly balanced.
And then we would, and there was a sticker on the actual reprint on the top that was yellow with black lettering that said this is an off-label use of X. The full prescribing information, please see whatever.
And just so it's prominent and it's permanently affixed, that article that is off label dissemination. And frankly, most of my clients that I counsel today do it just about like that. We're a little simpler version of what FDA's guidance says.
Remember, FDA's guidance is not binding, and I think it's a little over broad, but we meet the essentials. And my clients have never been in trouble doing it the way we've done it. And they've been doing it for 25 years.
Etienne Nichols
00:38:09.690 - 00:38:27.130
So, I'm curious if that makes sense how you, how you laid that out.
But I'm curious, what are some of the things that you see companies doing incorrectly, like maybe thinking, okay, well I'm just, I'm doing exactly like you know, Mark's described. But. And then you notice, well, you, you, you messed up here. Are there any things like that that you see?
Mark DuVal
00:38:27.690 - 00:39:41.259
And most definitely one thing that one big pet peeve for FDA is when you have a cover page. First of all, you don't say it. You know, you just start handing stuff out with any, without any disclaimers or disclosures at all.
And then they'll have a cover page that sort of does their distillation, sales distillation of what this article says. And some of it may be right on and some of them may be really off. And there's no fair balance. It's all about the benefits, nothing about the risks.
And that bothers FDA when it's done like that. There's a lot of ways you can mess. But FDA's got pretty understanding that this is the world we're in and that the first amendment does permit.
And look, we should want medical professionals to have the most recent information about products because it does help them make decisions.
Now what they don't, what they also don't like is when you hand out these glowing articles knowing full well there are articles that are in contradistinction and you're not handing those out with them or at least making people aware of that counterbalancing information. And that again, that's kind of violating the overarching principle of fair balance. Right? We want to State both the benefits and the risks.
Etienne Nichols
00:39:41.420 - 00:39:46.620
Okay, so that's dissemination. How does that differ from communication of on and off label?
Mark DuVal
00:39:47.340 - 00:39:52.380
Yeah, communication. Can I. Can. Is. Is it hard to put up a slide here?
Etienne Nichols
00:39:52.870 - 00:40:01.590
Shouldn't be. There should be a button between your. There's a video button and the gear button. There's a little square with a dot in the middle. Do you see that?
Mark DuVal
00:40:01.910 - 00:40:02.870
With an arrow?
Etienne Nichols
00:40:03.270 - 00:40:03.750
Yes.
Mark DuVal
00:40:04.070 - 00:40:04.710
Yep.
Etienne Nichols
00:40:04.870 - 00:40:07.830
That should allow you to find something in here.
Mark DuVal
00:40:08.790 - 00:40:13.590
Select a screen. Let's. Can you. Yeah, there it is. Can you see that?
Etienne Nichols
00:40:13.990 - 00:40:14.550
Yep.
Mark DuVal
00:40:15.350 - 00:43:41.080
So, this is what I'm talking about when we. This is the presentation. I think I made this one for convergence. It's probably the one you saw. So, this communication bucket is.
I talk about when it is informally again it's not written any guidance document, anything else.
But when it's informally safe harbor and when is it promotion and we try and help people and you know, we, we whiteboard and I'm just, I'll go there quickly and then come right back. We try and whiteboard, you know, with the possibilities for folks. And by the way, here's the slide on.
Excuse me that you were talking about the buckets. There's three and then there's a fourth now but let's go back. We help people whiteboard the ideas. But I talked about press releases for example.
You know, normally you can't just, you can't just send out a white paper that's about an off-label use. Your probably mail it out to folks. That would be illegal off label promotion.
But if you do it in the form of a press release as part of your public relations effort, there is some. The FD give permission to do that. There are things that you can do on the Internet.
For example, if people come up and talk about your product being in an off-label use, you know, you might, you might be able to join in that conversation. Say I just wanted you to know that this is an off-label use. And by the way, there are articles that address this.
If you would like to use then that, that would be maybe permissible on your websites you can have a repository for clinical data from and maybe other publications that address an off-label use of your product. Now if you had it on a banner page up front and you kept splashing use it for this off label use, that might be a problem.
But if it just came out you might be able to have a splash page. But then that has to go away eventually and then it gets relegated to the back room of, of clinical trial.
The library if you will so in all of these are opportunities to think through. You know, like everybody asks, can I train on off label uses and physician training? The answer is absolutely and unequivocally, no, you cannot.
But you are going to get off label questions. So, you have to think through, you know, how am I going to handle that?
And then a notice of availability, for example, is when you, you, you're going to, you want to advertise for. Because you're recruiting clinical investigators and there's FDA guidance on this. You want to advertise for clinical investigators.
And in that advertisement, you might have to juxtapose on one side of the page the on label uses for which it's currently cleared with the off label uses that you're seeking to enroll in a clinical trial.
And you're telling that, you know, the physicians, you know, maybe it's on the back of a cover of a magazine and you've got this ad and you're saying, we're recruiting for investigators for the following intentional, you know, use. Maybe it's for a spot back of a spine magazine or whatever. So, they're just, we try and help people be creative without violating the law.
And in fact, our tagline for our firm is we help you be appropriately aggressive, comma, yet compliant.
We don't, we don't feel people should unnecessarily leave money on the table, nor should they foolishly aggravate FDA and receive a warning letter and get told to cease and desist. So, we do have to help folks navigate that middle ground.
Etienne Nichols
00:43:41.320 - 00:43:49.720
I'm curious if you ever see exploding heads in the audience when you're teaching this, because it does seem, I mean, it's aggressive, but it's appropriately aggressive. And that's interesting.
Mark DuVal
00:43:50.120 - 00:44:40.040
No, it is. And yeah, I see it all the time.
In fact, a couple of probably three, two other convergence meetings when we were, I think we're in Vancouver, there were a bunch of FDA in the audience and I think they were taking umbrage and a lot of what I was saying, and I wanted to talk to them afterwards. I really love working with FDA. They are great people. Yeah, but you know, and their, their mission is different.
But I've never been in trouble with the agency.
We, A lot of times sometimes we'll even send them letters in advance about what we, how we're viewing our intended use statement and how, where we're promote, going to be promoting and to say if you disagree, let us know kind of thing. So, we work a lot with the agency and they're, they are Very good to work with.
They're not always, they're not always going to agree with you, but they're, they're good to work with. Yeah.
Etienne Nichols
00:44:40.360 - 00:45:30.100
And I think it's a fair and balanced approach that you have to, I mean they have their job, but we also, you know, everybody has their different perspective and job to work through that.
So, I'm curious again, so when you talk about these different off label uses or things that are maybe coming up and you're, you're putting those in, not necessarily on the splash on the front page of your website, but you're, you're hearing and getting more information from the industry about other uses of your product. There's got to be an approach or. Yeah, maybe this is a question.
What is the approach a company should take in regards to timeline to creating a new submission versus just continuing to sort of off, you know, go ahead and do this. Dissemination and communication of off label use. What about eventually a new submission? What are, what's, where's, what are your thoughts there?
Mark DuVal
00:45:30.500 - 00:51:41.740
Yeah, well, a lot of times, especially in the 510(k) world, well, even in the de novo world, we often are counseling clients if they don't have the money or the financial wherewithal to go for the home run at the beginning with the big indication that they really think this product deserves and will serve. A lot of times we just say let's just do a two-stage strategy.
Let's get you on the market for a more limited claim and start generating some revenue so that you can pay for the longer-term clinical studies to put the product in the segment of the market where you really want to be, which is also the largest or the most lucrative or whatever. So, we work with companies all the time in regulatory strategy. Again, we asked them to begin with the end in mind. What is it you'd like?
What in an ideal world, if you could say this is what I want to sell the product for and then let's work our way back to reality. Sometimes that is reality, but sometimes it's not at all reality and we have to work our way there. I'm giving an example on coaxia.
A company I worked with, tremendous company, got two 510(k)s and an HDD for cerebral vasospasm and then were headed for a PMA because they wanted the product which was straddled the renal arteries and dual balloons that when inflated with straddle the renal arteries and direct redirected blood flow, the upper extremities, the brain, the heart and the lungs. Really cool product and an evolution in the next evolution in the line of products that were there at the time.
And they wanted to get another PMA, and they had a 515 patient study and the, the efficacy was there or wasn't. Excuse me, the safety was there on a two to fold one margin. Its efficacy just missed, barely.
But they accepted an endpoint, a return to normal for an ischemic stroke patient, which wasn't very realistic, but yet they almost hit it, but they fell short. And so, what do you do? You get a 515 patient study, you've nailed safety and then you've got effectiveness, which just has fallen short.
So, on a PME basis you're not going to get the claim that you wanted. So they backed down and they came to us, and they tried to get a 510(k) and they failed on that.
And then I was hired to argue that on appeal to get them their 510(k). And we came up with a compromise which at the time I thought was good. It was like 11 years ago now. And they ex, they did it.
Dr. Maisel offered a de novo panel meeting which in retrospect was the biggest mistake could ever make.
And the reason is when you're in a, when you go, when you hand a device to a panelist, a PMA type panelist and FDA have these folks that they use repeatedly, they think they're lost in a world of biostatistics and they think big, right? They think PMA, they never can dumb down the framework. I just did a 510(k) panel meeting a year and a half ago, same thing.
They could never think in the, in the framework of the 510 program or in the case of coaxia, the de novo. And they could never look at the probable benefit has to exceed the probable risk.
And it's a, it's a lesser standard than the, than a true PMA for It's a Class 2 moderate risk device.
And we tried to explain that and how you have special controls become a surrogate for the establishment of reasonable assurance of safety and effectiveness. And we really tried to explain that to the panel kind of to no avail.
They could not divorce themselves from this grandiose, very, very granular, biostatistical look at the data. So that's an example. So, we, we were trying to say, look, this, the 550, this data has substantial worth.
It's a 515 patient study following on two 5 10ks in an HDE, this product. All we were trying to say is it could be used with, not necessarily to treat ischemic stroke patients is a very modest.
And we gave them an example of another predicate that had done a similar, at a similar type of claim in a very closely aligned therapeutic segment. But the FDA, you know, the panel didn't buy off on it. The FDA didn't buy off on it.
And you know, Bill and I still need to have a talk about what happened at that panel meeting. I consider Bill, I really do consider Bill a great friend. He's a, he's been a breath of fresh air to the agency ever since he's gotten there.
And I said at the MDMA meeting a couple weeks ago, talking about the De Novo program with Peter yang, who's the D.O.
program lead for de novo at CDRH, I said to the audience, you know that Dr. Maisel, we really appreciate the fact that you take appeals and you do overturn staff from time to time and when you don't overturn them, you find compromise because you're teaching them as you do that you're teaching them. And that is now cascaded down to some of the office directors. Not all.
Some of the objectives are very Maisel like in their decision making they're very fair minded. They really apply the law and the guidance, regulation, guidance strictly and fairly.
And it's even seen it trickle down to some of the, you know, what we would call branch chiefs. They're called division directors now.
And because we can't have all these decisions funneling up to Bill Maisel and he's been deputizing Owen Ferris to hear some of his appeals. But it can't, it can't, all of it can't go there.
We need push it down and hopefully the training on the Contours of the 510(k) program, definitional elements will get down to the review staff. The review staff are getting smarter about that, knowing it. But they take a position and they're not open minded.
Once they've taken a position and it's usually conservative, they're locked in and you're not going to move them at all. And probably not the division director either. And so you're on a path that has to take you up.
So, we try and get involved really early on in 510(k)s if we're not submitting them ourselves to help people understand, to give kind of strategic direction, I.
Etienne Nichols
00:51:41.740 - 00:52:03.440
Might ask like just maybe a tweak on the question I asked.
So, suppose a company is they're already commercial but then they start to detect other uses out there, maybe off label and They're I guess it's a business decision. I guess it would be to determine an ROI decision to determine whether or not they want to have a new submission.
Is that the thought there in that situation?
Mark DuVal
00:52:03.680 - 00:52:38.800
Yeah, no, absolutely.
It's financially driven and sometimes they're doing just fine just leaving the product where it's at and let them the off-label use if you will become commonplace. You know that's for most off-label uses are discovered anyway. It's by the medical community says hey if it is beneficial here, I can extend.
I apply a medical extrapolation of logical medical extrapolation to apply it over here. But and sometimes companies say, you know, I don't, I just we need to get this on label so that we can actually promote for this use.
Etienne Nichols
00:52:39.200 - 00:52:50.160
That makes sense. Another thought is so I know Europe requires a little bit more real-world data.
I'm curious if FDA is moving towards that a little bit as well or do you have any thoughts around that?
Mark DuVal
00:52:51.740 - 00:55:58.960
Yes and no. And Dr. Shern, just recently I basically had an appeal ongoing, and it was a little bit.
It had been decided by Bill Maisel, remanded if you will to the office director. So very high-level person, 1 of the OHT 1 Office of Health Technology people. It wasn't one, it was one of the OHTs.
And so, he in a sense acted like all a judge would do. He decided the case, if you will in our favor then remanded it if you will down to be handled.
And then the trial court judge, if you will or the office director didn't handle it so well. And so, we one of our people with the regulatory affairs person from the company was on. He was actually a consultant for the company.
Saw Dr. Sheeran at the speaking at one of the conferences and afterwards he got first in line. She said Dr. Sherman, we have this situation that we're stuck, and we've offered real world evidence.
And you spoke glowingly and how important it was to the agency that you're really going to move there and whatnot.
But you know, and he said, you know, fortunately he got tangentially involved and just called, you know, got Bill involved again re involved and it's all resolved itself. But the point is the FDA talks a lot about real world evidence at the Sheeran mazel level.
And you know when they're talking to the public and the Congress and whatnot. But when you're in the trenches day to day trying to convince them to use something that's real-world data is work.
It can be done though and we have done it, but you've got to be really particular.
And what they're really concerned about, of course with real world data is if you're retrospectively dredging up data, they want the study design for the retrospective data de dredge if you will, to be prospectively designed and to do its very best to eliminate bias and cherry picking of data insights.
And you know, because you've got data out there where people have been using the product, they might have medical images that can be harvested and good data that you know, OS indexes that have been filled out or whatever, there's you know, radiographic data images, there's a lot of stuff that, that really can be good and then you can use it. The FDA wants to know it has, you know, that it has some integrity and they truly are getting better.
And in pre submission meetings they're getting pretty good at helping us.
We, I had one cardiovascular client where we actually negotiated a real-world study against an index or a registry that's been going on for decades or a decade at least. And we're gonna be able to compare against that. And I'm really excited to propensity scoring data.
It's really exciting and the FDA is really working hard with us and it's, I'm very proud of them. It's Bram Zuckerman's group.
And so yeah those, there's success stories but there I, I think we gotta get the desire to accept real world data from the top-level folks down to the trench level folks and middle management.
Etienne Nichols
00:55:59.840 - 00:56:17.920
Okay, yeah, that makes sense.
Curious if you have, before we go to Q and A, do you have any other thoughts, Recommendations for regulatory affairs professionals, med tech professionals, an approach to ad promo? Just the any general advice that you typically hear questions on. Any thoughts?
Mark DuVal
00:56:18.240 - 00:58:15.940
Yeah, I think your management will value you. They know you know the regulations and the law and what.
But where they're really going to value you is when you can become creative and help them get to their goals. So, and you know, firms like us are here to help you. But even some, I mean I know some law firms that are still as conservative as FDA.
I just think you need to just open your, your mind and think there if is this possible, ask the question is what they don't just be immediately dismissive of sales and marketing saying here we go again. You know, they're always pushing the envelope or whatever. Just ask yourselves, I'm not going to be so negative about this.
I'm going to ask myself is this possible? And then if you don't have it, you know, you don't know if it is on your own. Get help. And there are folks out there can help you brainstorm.
And that's like I say, that's why we do these whiteboard exercises all the time, because we literally will sit down, I'll go out to a company, and I'll do a didactic for two hours. And what's the landscape that they're going to encounter in advertising promotion from an enforcement standpoint? What are the FDA's expectations?
But when I say be truthful, not misleading and fairly balanced, that's the framework.
But there's a lot of stuff that comes out of, in the regulations, in the guidance documents, in you glean from warning letters and all sorts of stuff that tell you what FDA's interpretation of things really is. But if you, if you whiteboard, you know, we'll do, like I said, we'll do a two-hour didactic, we'll do three, four hours.
I'll just say it to the marketers, throw it all on the table. What are your ideas? Let's whiteboard stuff right now. What would you ideally like to do?
And let's start, let's start the path on figuring out how we can do that. We've done that. We've had 1254 clients, so we. Not all of them have been advertising promotions, some of us on the submission side.
But, you know, I, you know, I, we probably have an N of 800 on this, so that's pretty good.
Etienne Nichols
00:58:16.900 - 00:58:29.700
And one last thought on that. So, you'd mentioned the general and specific use. I wonder if you could maybe just. I, I know you have a good illustration of the umbrella term.
I wonder if you can just kind of dive into that in the next five minutes.
Mark DuVal
00:58:29.700 - 00:58:33.940
Yeah, yeah, I can even go up there and do it. Am I making people dizzy doing this?
Etienne Nichols
00:58:33.940 - 00:58:36.300
I threw you all over the place. Sorry to do that to you, Mark.
Mark DuVal
00:58:36.300 - 00:58:39.690
That's all right. Right there. Right.
Etienne Nichols
00:58:40.890 - 00:58:44.610
And if you're okay with it, we'll provide these slides as well, if people are interested.
Mark DuVal
00:58:44.610 - 01:02:49.860
Okay. Yeah. Well, these are convergence. So let me put the opening slide for you.
I'll recreate the opening slide, so it's not stolen from wraps technically, but so here's where FDA starts. And you know, we never had these two definitions before FD's to talk about. And people still confuse intended use versus indications for use.
Technically, the statute and the regulations talk about intended use, which just is nothing more than the general purpose of the device or what it does. And then it encompasses the subsidiary Indications for use.
And the indications for use then is defined to mean the disease or condition the device will diagnose, treat, prevent, cure or mitigate, including a description of the patient population for which the device is intended. I will note one thing here, notice the word treat here. And so, I'll show you some, some stuff here in a minute.
The difference between tool and treatment. FDA gravitates in the 510(k) toward a tool, but frankly they do allow you to say something about what it treats. And so, they have trouble.
I have a recent case appeal that we won at the office director level where they have now permitted us to use basically a treatment test type of claim. It's hard to this without giving away. I can't describe it, but this is what you were looking at. And it's from one of our client alerts.
I've been using this umbrella for, gosh, at least 20, maybe 25 years to describe. And you know, and Marjorie Schulman, FD, used to use this.
Director of the 510(k) Program Operations Staff, she just retired, but she used to give me credit from the audience when I was in the eyes for this because I used to, I've always thought this. I, I always think visually, guys, just, you know, I think of the general intended use as being the umbrella.
This is the umbrella that you were handed by FDA.
And I'm fond of saying that FDA is fond of giving you a general intended use statement that suggests the product can be used for just about everything. But then they tell you that you can promote it for nothing. So, it's very difficult, it's frustrating for marketers.
And so, the umbrella contemplates a lot of subsidiary indications for use that would be on label indications. If you think of the rain, the umbrella protecting you from the elements, you're under there and you're staying dry and you're okay.
But if you get too far afield, you're out there on the edges of the umbrella, you're exposed to the elements, you're off label and could get a warning letter. And certainly, you probably have to do a de Nova or PMA to get that, that indication.
So, the way FDA breaks it down is analytically, is it one old guidance document plus their 2014 510(k) guidance document, but they have this old one that they still use. It breaks it down into levels of specificity. How specific are you getting with your claim?
All the way from identification of a function like cutting down to an effect on a clinical outcome. And then the second one is, are These decision-making criteria and there's seven of them and they look at risk, they look at public health impact.
In other words, how much more risk does the specific use entail versus the general intended use? They look at the knowledge base of the medical community, can they use the specific use just like they would in the general.
Doesn't change what endpoints apply to your studies that you've done or the data you have applied to specific use.
And then this famous tool or treatment one, you'll see this in warning letters, you'll see it in ainn letters, they'll come back to you, and you think well we think you're really making a treatment claim and if you are, you have to, you're going to be a de novo or whatever. So that's kind of where FDA goes with it. The example, classic example is the ablation devices. They first were used cleared to ablate soft tissue.
That was the umbrella. Then they started saying well we ablate cardiac tissue, now that's on the edge of the umbrella.
And then they started saying well we're used to treat atrial fib. And that got you out in the treatment realm. And that was off label. And FDA retrenched and said oh timeout, we've gone too far. So that's.
Does that help answer that question?
Etienne Nichols
01:02:50.180 - 01:03:04.840
Yeah, it does. And I guess one of the other questions maybe follow up is why would you want to be very specific with your indication of use?
Would that be to reduce some of the testing load in the submission or what are some of the reasons you might want to do this versus that?
Mark DuVal
01:03:05.160 - 01:04:45.240
Absolutely. So, at the de novo program I talked about being tethered to a poll. You know, 510(k) to the FDA is like being tethered ball on a tether pole.
They can only ask for data. You can only in the sphere of the, the potential sphere of the, of where the tetherball goes is in the poll is the predicate.
They can't go; they really shouldn't be going any further than the predicate did. And they're often trying to do that. They're all.
Their FDA is often trying to shore up predicate families by asking for clinical data that has never heretofore been asked, requested or maybe biocompatibility data beyond which has been requested or bench testing animal data, whatever. They'll ask for more and more and more, almost analysis, a mindless escalation of data requirements.
And when you get them to think about it, they and you say hey, we're in the 510(k) and here's what the predicate families established. You have a under least burdensome requirements principles. You have a strong argument to argue them down in A and to stay tethered to tethered.
If they get you, if they define you off the 510(k) path and you're in the realm of de novo A. I hate to say this, they say they would be biased by user fee economics, but they get about $100,000 more and they aren't tethered to the poll anywhere. Now they're in the realm of PMA land. It's reasonable assurance of safety and effectiveness, albeit applied to a Class 2 moderate risk device.
So, it's kind of a PMA lite standard. It's more than a 510, but less than a PMA. And so that's what, you know, that's what's transpiring there. Okay.
Etienne Nichols
01:04:45.390 - 01:05:02.110
Yeah, that makes sense. Well, this is great.
I know we're kind of at time for, you know, this section of the podcast, so I really appreciate you coming on the show and yeah, I'm excited for future events. I know we; we have TQR True Quality Roadshow coming up in Minneapolis with Howard Roots. I'm really excited to see you in person there.
Mark DuVal
01:05:02.190 - 01:05:05.230
So yeah, thanks again, Mark. You're welcome.
Etienne Nichols
01:05:06.270 - 01:05:40.100
All right; I'm just going to give a little pause so we can have that recording kind of edited towards the end. But now we have some questions from the audience. I really appreciate those.
I know there's a whole lot more you could go through, but let's look at what the audience had to say. So, there were a few things. Let's see.
Zach asked if a physician uses a product in an off-label fashion, could a case study of or marketing document be created around the off-label use of the product? As long as the information presented is truthful, not misleading, fairly balanced, and provides disclosures, disclaimers that, you know what, I.
Mark DuVal
01:05:40.100 - 01:07:10.880
Think it's a great question. Happens all, we get it all the time. So, case studies are interesting. Yeah, we do allow clients to use case studies. We figure out how they can.
Oh, you're putting it up for me. That's helpful. But physicians, you know, or companies want to use case studies all the time.
You know, you know, if you, if you're just doing an N of one case study and it's on an off-label use and you're kind of touting it, that's, that's pro. That can be problematic.
But if it's part of your publication planning and you're Working with physicians and they decide to start publishing stuff that's you know, and then you start drawing. You can point people to it. That's, you know, that's an opportunity to market lawfully.
But onesies and twosies, case studies are more difficult sometimes companies and by the way, I can't give legal advice here, so I have to be careful, you know, unless you're a client. But, but you also wanted.
Sometimes people are putting on, they have a case study series and they're asking for physicians to contribute to a venue that they've created.
But the physicians are then allowed to say whatever it is they want, and the company puts on a major disclaimer or as an overlay onto that whatever the. And then they don't edit what the. You know what the. Except for to make sure it fits within certain parameters.
They don't edit what the fish physician has to say about a case study.
There are a lot of, there are a lot of things Zach, that you can do in that realm, but it turns a lot on the facts and how you get it done correctly, for lack of a better word.
Etienne Nichols
01:07:11.440 - 01:07:34.410
Yeah, all right, thank you for answering that. Don has another question. You might have answered this one. Regulatory submissions are tied closely with the clinical trial strategy.
A growing demand exists from the FDA for real world evidence, real world data. What's your view on coaching the clinical strategy again with the end in mind for those these to be accomplished?
Are real world evidence and real-world data helping or hindering regulatory submission reasonableness?
Mark DuVal
01:07:35.850 - 01:09:39.860
Lawyer's answer on that is both. And actually, that'd be the regulatory affairs answer on that is both. It really.
So, I'm going to go back to that concept of not just file thinking of a submission, whether it be a pre submission filing, whether it be a 510(k) or de novo where it be a response to an ain letter. Everything is it just. It's not just an evidentiary document. It's an advocacy document with evidence. Our RWE, RWE or D is never going to sell itself.
You're going to have to sell it to the agency and a lot of times if you it it tends to be confirmatory.
So, it might be a fruitful discussion for a pre sub but sometimes even psychologically I wouldn't want to offer it up front because you'd want to see if you could get by on the data you have but then be prepared to come back.
Well, what if we offered you some real-world data and then sometimes, you know, you're presumptive about your position, you've already done it and you're submitting it and hopefully it's good enough. But in FDA's psychology they rarely. You got to understand the psychology of a regulator.
Most often whatever you provide on the first pass is not good enough. They cannot help themselves. It's just not going to be good enough. And you have to either convince them or provide additional information.
And when you provide additional information, of course the preference for them to say is, well, you need to come to us to ask us precisely what additional information you might want if it's going to be in real world data.
And sometimes you have it already done and, in the bag, and you just want to, you didn't want to give it to them up front, but now you want to give it to them as confirmatory information. So that's a big topic, Don. And Don's a friend of mine, by the way. That's a big topic.
And we spend a lot of time with folks strategizing what's the best sequence, what is the best, what's the quantum, the quality of data we want to file, what's the best sequence to do it and do we want to go to the FDA to flesh it out how we get it or not. So, it's a big topic.
Etienne Nichols
01:09:40.180 - 01:10:06.360
Okay, no thanks. And Don, thanks for putting them on the spot there. So, Jasmine has a question.
She's asking about the use of contract sales forces or Medical Affairs MSL for engaging HCPs and she asked how can compliance monitor sales, particularly in the context of contract salesforce? I think how can they monitor sales?
And commercial or even medical affairs are not soliciting requests for off label information and promoting off label.
Mark DuVal
01:10:08.040 - 01:11:49.150
Yeah, well, first of all, it starts with the contract, and I used to be a general counsel so I would put it right into the contract.
There's like this, there's this wrong presumption I think on the part of some a, there's a wrong presumption on the part of a contracting organization that, you know, you can't engage in compliance with my organization, which is completely wrong. Not most don't have that view, but. And then there's a wrong presumption on the side of the company.
That FDA doesn't hold us responsible for the acts of a contract employment employee. They most assuredly do. So, you really are going to have to work out. Just treat them like you have to in a sense kind of treat them like this.
Your sales force, you have to bring them in. I remember working with Medtronic software Danic and they had six.
I used to train annually 600 folks at a time, and we break it down in like 125 a piece and do you know, segments and when we did that though, we, we, I, Medtronic is like this. They just said if you're a contract employee working for us, you are basically us because you're representing our name.
And so, you're going to get all the training our sales reps would get and you're going to have to adhere to the same policies that we have in place about off label dissemination and pricing bundling, and rebate offers and whatever else it is. We want you to make sure that you're following company policy now. The smaller you are, the less clout. You have to insist on a lot of that stuff.
So, but you have to, you are going to be held responsible. You got to find a way. And usually, usually company, the contract organizations are good enough to know that today and they're not too bad.
Some, some are horrible, but most are pretty, pretty decent about it and they will show up at your national sales meetings and things like that.
Etienne Nichols
01:11:49.950 - 01:11:54.950
So that's really one of the biggest takeaways for me is you still have the same responsibility for their actions.
Mark DuVal
01:11:54.950 - 01:11:56.430
Really? Yep. Yep.
Etienne Nichols
01:11:57.310 - 01:12:05.350
William asked a question. Can you talk about the FDA versus FTC related to ad promo and when we may trigger enforcement action?
Mark DuVal
01:12:05.910 - 01:12:57.820
Right. That's a fantastic question too. First of all, they have competing jurisdiction and they have a memorandum of understanding that allows them.
And FDA has ceded a lot of authority to the FDA because it's a lot of their. Because the FDA is the one that's granting permission to get on the marketplace. Right.
So, they have had intense negotiations on intended use, indications for use, etc. On a 510 they can't talk to you about your advertising promotion, constitutionally speaking, or even a statute.
But on a PMA, they have that right to even talk about the launch. And it's true with a new drug application as well. So, there's more authority on that end of the spectrum.
But where you're down on the 510 end of the spectrum of de novo, they don't, they don't have as much jurisdiction and authority over. But do you, can you post, actually post that question?
Etienne Nichols
01:12:58.300 - 01:13:00.860
Let me see if I can. That's in a different section and I.
Mark DuVal
01:13:01.260 - 01:13:08.260
So just go back to it again because I was, I got off tangent and I want to make sure I'm answering the question. Just read it again. That's okay. Yeah.
Etienne Nichols
01:13:08.260 - 01:13:11.180
Can you talk about the FDA versus FTC?
Mark DuVal
01:13:11.500 - 01:15:10.130
Related. Yeah, yeah. So, FTC. So, FTC.
Though I've got a recent example, two recent examples where we were dealing with a company on nutritional supplements where we were trying to close out a warning letter that we had for clients that came to us after getting a warning letter and we helped them out.
And it was interesting because while we got a release of the, we got a close out of the warning letter from FDA, the FTC wouldn’t, and it was really strange.
And we've been skirmishing with them a bit on this and saying, you know, the common opera, there's a common operative set of facts and there's similar but not identical statutes. Certainly, it's about getting, making sure that products are being represented truthfully, not in a not misleading and fairly balanced fashion.
And yet FTC was getting, you know, I think this new administration under Biden is actually being a little more aggressive with FTC.
You can see them trying to work on non competes and things like that, saying that they want to have a national rule which they can't do that you can't have non competes throughout the country in contract, you know, employ independent contractor relationships, extend that kind of liberality, that thinking to what they seem to be doing in advertising promotion. They seem to be wanting to get a little more active on what has historically been ceded to FDA as their turf. So, this is yet to play out.
I don't know, we don't know where it's going. But they technically do have jurisdiction authority.
They don't give it up in the, in the arenas of Class 1 products, especially where FDA is a little light, you know, all you got to do is register and list your product and register your establishment, list your product. So, on class one products that are, you know, low risk and usually 5, 10 exempt, the FTC will jump in a little bit more.
I've got products on this shelf behind me where we've represented class one product where FDA has taken a little more pronounced, prominent role. So, it's evolving. It's a great question.
Etienne Nichols
01:15:11.170 - 01:15:40.140
Interesting. And another question is kind of about your thoughts about maybe the 510 program. I know it's evolved over the years.
There are certain some people from, you know, on the consumer side or the medical side feel like it should be even tighter than it is.
I know there's documentaries like the Bleeding Edge that talks about those things, but then also from the industry there's the tension of, well, it's, it's too restrictive. What are your thoughts? Is, is there any change in the future? And if so, what would that change look like? Do you have any?
Mark DuVal
01:15:40.580 - 01:19:11.970
Yeah, well, you know, I know the bleeding edge and it's funny because those people really don't know the amount of data that you submit and then the level of negotiations that take place and the quality of the data that gets them and if it's not of quality and make you go back and redo it, frankly. So, I used to, you know, I used to laugh when plaintiffs’ lawyers would gin up, you know, and they talk about how the 510(k) is just this me too program.
And frankly, you know, in the early years that there were, there wasn't a lot of data, and you could basically prove you're on the market by virtue of a pre amendments device and beyond. And then There were early 510(k)s and the lineage was not; the program was not applied that aggressively.
But technology was not even on an incremental basis improving as fast as it is today 510(k)s are.
And when Dr. Shern came into office as the center director, the first thing he tried to do with the Institute of Medicine was dismantle the 510 program.
Now he's, he's a bureaucrat, he's an administrator, he's not a legislator, but he was kind of acting in a quasi-legislative capacity trying to so radically change the 510 program. There was a human cry out from industry, and I was part of that.
And he did back down, and I give him a lot of credit and he's now working with the 510 program. But here's what's happened is they continually get more and more conservative on how they're defining the 510 program.
And they can, it's, it gets easy for them to define products off the map and get them out of the novo path where they do get $100,000 more per submission. So, it's a lot of money. Now I talked to Peter Yang who I said this question may come up for you.
And in fairness to Peter, he said, mark, honestly, we are not motivated by that. We just, we think of it as submission of submission.
We don't think in terms of the money that comes in because we're just, we're working on, we're too busy. We're just working on stuff at the review level. And I take him at his word.
But I, you know, upper management, Ben is the beneficiary of that because they're always asking for more money on behalf of the organization. And I just want us to be really have some degree of fidelity to what Congress really intended.
So, my job is when I go in, when we go early on in, you know, we're a big fan of executive summaries. When I talk about an advocacy document. Start out, folks, telling your story.
The executive summary is probably the most important part of your submission, of your response of anything that you do. And I always say that people always speak. And I've media trained many, many times at 3m. People always speak in the form of an inverted pyramid.
Think of it. They ramble, ramble, ramble. Get to the point. Yeah.
And then media trainers will tell you, flip that around, get to the point and support it with an increasingly widening base of information and explanation. And that's what your executive summary is.
It's to distill down for the agency what this product is and where you're headed and why you believe it's deserving, for example, to stay on the 510(k) path and anticipate proactively that they might object to. Yeah, you don't have a predicate, you don't have the same intent. So, you don't.
You have different technological characteristics and you're raising different questions of safety and effectiveness. And we, we have argued this so often. We have a lot of creative and solid arguments about how to defeat those. You know that.
Those arguments from the agency.
Etienne Nichols
01:19:12.450 - 01:19:38.790
Yeah, that's great, great answer. I appreciate that. Melinda asked a question.
Maybe we'll make this the last question just so people have a few minutes before, you know, whatever the hour comes. So, Linda asked the questions.
Any thoughts on the best way to word contractual agreements in relation to CPG 300, 600 for capital equipment like an MRI machine that have frequent changes to its software and to use functionality that assures the customer when they purchase it they'll be entitled to future upgrades that.
Mark DuVal
01:19:38.790 - 01:22:28.320
Technically don't exist yet. Yeah, that's in the chapter of my book.
I was a kind of specialty of my, my colleague that wrote that, the chapter, whether we wrote it together, it's basically, you know, what are you doing when you're, when you get next generation products that are changing, particularly. So, if I got this question right, Melinda, things are changing, and you want to incorporate that in. When does it become a new device? Right.
And so, when do you have to. And that gets to FDA's modifications guidance, which was put in place, I think in 2017.
I believe you might remember though, an FDA put in their into place their modifications guidance document, their original request that we in an industry fought against it because even AdvaMed and MDMA fought and basically saying you're basically going to be asking for several hundred thousand more 510s a year.
Because if you take all the changes we make to devices and they are going to be the subject of a brand new 510 under the new modifications reading of your modifications guidance, you're wrong. And the statute, basically simple, can make a modification to a device, does it significantly affect safety or effectiveness and.
Or has it been a major change to the intended use? And FDA's guidance goes way farther than that. And they put it into the risk benefit analysis.
And it's not totally true to the statute of the regulations, but it's not that bad. The point is, with respect to capital equipment, if you're making changes, when do you have to file, you know, for a new 510(k)?
And when can you just do a letter to file? And we often author letters to file if we think they're going to be a close call.
And the, and we want that investigator to pick up, when they pick up that memo, it says Duval and Associates at the top because they don't usually mess with us like they would if it's an internal memo. But don't just do, when you change a product, by the way, don't just do a narrative or don't just circle the. The flowchart.
Do a narrative to accompany that and convince them again, it's an advocacy document. Now, going back to her question on contractual language, Melinda, that's a very specific question.
You know, we'd have to spend some time, but yeah, you have to, you do have to address that because you can't be selling products before they're actually cleared. And the reason I talked about the modification’s guidance document is that's the step before you have to decide whether you need a clearance or not.
Is it an LTF or is it a clearance?
And if it's a clearance, then you have to be, you know, FDA has gotten a little more accepting of what changes can be made to certain devices, particularly software driven, because, you know, there's always bugs that have to be worked out. You can't file a new 510(k) for everything. So that's a, that's a very intricate and important question, but I can't answer it completely.
Etienne Nichols
01:22:29.490 - 01:22:39.170
Yeah, in this format, I'm sure it keeps going. If you have multiple letters to file, I'm sure at some point, you know, maybe having an aggregate of the changes. Yeah, there's a lot there.
Mark DuVal
01:22:39.330 - 01:22:46.130
Absolutely. So that's the predicate family grows and grows, and you have to do a catch up 510(k) at some point.
Etienne Nichols
01:22:47.010 - 01:23:01.330
Well, this is really, really interesting. I really appreciate it, Mark. I think we're going to just go ahead and cut it off now. Those are some really great questions.
I appreciate the participation from the audience. Any last things you'd like to say, Mark, before we let you go?
Mark DuVal
01:23:01.970 - 01:23:15.970
No, this is a really fun format.
I've never really done a format at this length, and I really appreciate walking me through this and helping me technologically figure it all out and then enjoying some time answering questions from the audience.
Etienne Nichols
01:23:16.370 - 01:23:27.390
Yeah, this was great. Well, thank you so much. We'll let everybody know when the recording comes out so you can share it and let's do it again.
Really appreciate everybody's participation. We'll let you all get back to it. Take care.
Mark DuVal
01:23:27.710 - 01:23:29.150
Thanks. Bye Bye.
Etienne Nichols
01:23:30.750 - 01:25:59.810
Thank you so much for listening to this episode. A few of the points that I took away from this conversation are 1.
We talked about that 4 buckets of information sharing at the beginning and then throughout the episode. And they all have their place.
Number one, the first one being promotion of on label information, whether it's general or specific use, the dissemination of off label medical scientific information and then the communication of both on and off label information. And then the last one which he says is relatively new, the promotion of off label information. So fantastic takeaways.
I really enjoyed the four buckets of information that he shared. One of the biggest things to think about is that the information you provide has to be three things. Truthful, not misleading and fairly balanced.
He said if you listen and you hear and remember anything, remember that the things that you share have to be truthful, not misleading and fairly balanced. Fantastic.
I also loved his umbrella analogy, which if you haven't gotten a chance to get over to Duval and Associates and sign up or subscribe to their client alerts, this is inside one of those client alerts. It's a very well-done publication that they do and provide to their clients. He has an umbrella analogy.
The point is that your on-label indications should stay under the umbrella of your general. There's so many links in the show notes, so be sure and check those other resources out. We shared guidance documents.
We shared a link to Howard Root's book, which I'll be interviewing Howard Root in Minneapolis in a few weeks at our True Quality Roadshow. So, if you haven't got a chance to check that episode out, likely by the time you hear this, it will have been released. So, check that out as well.
If you enjoyed this episode, reach out to Mark DuVal on LinkedIn. Let him know. Also, I'd personally love to hear from you via email. Etienne Nichols, Greenlight Guru or look me up on LinkedIn.
Let me know if there are other specific topics that you'd like us to cover or specific experts you'd like us to interview so that you can hear more from them.
Lastly, if you're interested in learning about our software built for MedTech, whether it's a document management system, CAPA management system, or an electronic data capture for your clinical investigations, or your design, controls and risk management software, let us know. This is software that's built for MedTech professionals by MedTech professionals. You can check it out at www.greenlight.guru.
Lastly, please consider leaving us a review on iTunes. It helps others find us and it lets us know how you're doing, how we're doing. I hope you're doing great. Thanks again. You're the best. Take care.
About the Global Medical Device Podcast:
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