In a continuation of the previous episode, Mike Drues joins the podcast to further discuss LDTs, IVDs, and how those related to the ongoing Theranos situation.
Mike is the president of Vascular Sciences, has a Ph.D. in biomedical engineering, and has extensive experience with Regulatory Strategy.
In today’s episode, he begins by reviewing some of the information in Part 1 of this discussion. He discusses how the current regulations and language around LDTs relate to the Theranos situation and what companies should be doing to ensure they’re ready when the VALID act goes through.
Listen to this episode to hear what Mike has to say about the risks of LDTs, the engineering work that should go into LDTs, and how the regulations could be changed to close the Theranos loophole.
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Some of the highlights of this episode include:
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The risk behind LDTs vs IVDs
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Whether LDTs belong in the IVD category
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The relationship between the LDT situation and Theranos
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Principles to use with LDTs
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What companies should be doing now in anticipation of the VALID act
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The importance of a contingency plan
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The criteria for a legitimate LDT
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Specific parameters to define an LDT
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Labeling
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Technology
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Risk
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Requiring hospitals to put LDTs through institutional review boards
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Better oversight
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Creating a EUA-like pathway
Links:
Memorable quotes from Mike Drues:
“Even from a technology perspective, the technology of these LDTs is becoming much much more complicated.”
“Long story short, I think Theranos took a fairly liberal interpretation of the words surrounding the LDT.”
“I’m a biomedical engineer first and a regulatory consultant second. And that’s the order we should think about these things.”
“Even though I’m a regulatory consultant, I’m not a fan of creating new regulation.”
Transcript:
Etienne Nichols: Hey everyone. Welcome back to the Global Medical Device Podcast. My name is Etienne Nichols. I'm the host of today's episode and with me is Mike Dreus, a familiar face on the podcast.
Mike, how are you doing today?
Mike Drues: I'm well, thank you, Etienne. And how are you doing?
Etienne Nichols: Well, I'm excited to talk a little bit more about LDTs. And just to give a quick reframe or a context here, we had talked a little bit last week in our last episode about lab developed tests and I think we titled the podcast “Closing the Theranos Loophole”.
Should that loophole be closed? And maybe we talked a little bit about what that means. But I wonder if you'd be willing to give a bit of a recap and maybe we can, you know, pick up where we left off.
Mike Drues: Yeah, happy to do that, Etienne. And as always, thank you to you and your audience for the opportunity to have this important continuation of our discussion on lab developed tests.
So, a couple of the high points that we talked about in part one.
First of all, why are we talking about this subject now?
And as we briefly mentioned last time, one of the things that the Congress passed in December was FDA's budget for the coming fiscal year.
Unfortunately, though, one of the things that was not in the budget was the verifying accurate leading edge IVCD or in vitro clinical tests called the Valid act. I know that's a lot of words and a lot of syllables, but basically the that would have given the FDA the power to regulate laboratory developed tests.
Suffice it to say, that did not get passed, largely because the argument was made, whether we agree with it or not, that requiring labs to do this through the FDA would be too burdensome. We can talk more about that.
But that was the justification and the reason why LDTs are not regulated today, which we also talked about in more detail in part one, is because philosophically, an LDT is supposed to be a type of in vitro diagnostic or IVD that's developed and used in one particular laboratory or clinic or hospital for use only in that laboratory or clinic or hospital.
And this has been the justification for decades why FDA has not regulated them. Because one could easily argue that that is the practice of medicine, something that FDA does not regulate.
Just like pharmaceutical compounding, just like reprocessing of reusable medical Devices, just like even in some cases, 3D printing.
So, it's just another iteration on the, on that scene.
So those are just a few of the highlights that we talked about in part one. Happy to go into that in any more detail, Etienne, and. Or we can continue on to some of the other topics here for part two.
Etienne Nichols: Yeah, and one of the things that I remember you bringing up when we talked about the LDT, not.
It's not LDT versus IVD. That's a bit of a false dichotomy. It's more because if you have an IVD that is then altered by a lab, for example, it becomes an LDT, if I remember correctly.
So that being said, I think it's interesting to maybe, maybe we could dive into the risk that is associated with LDTs, because there is a bit of an assumption when we use the phrase LDT versus IVD that there's a difference in risk.
And I wonder what your thoughts are when it comes to the risk of one over the other.
Mike Drues: Yeah, great question. And just to remind you and our audience that I happen to be a subject matter expert for FDA in a few different areas, one of them being risk.
So, this is a topic, you know, sort of near and dear to my heart, so to speak. So, another part of the historical justification for why FDA has not regulated LDTs in the past, in addition to the practice of medicine argument that I made a moment ago is that historically, most LDTs were quite, quote, unquote, low risk devices.
In other words, they were often using very, very well-established technologies. There was nothing new.
They were not intended to diagnose, treat or prevent a disease, injury or condition. In other words, they were just simply measuring a substance in a sample from a patient. Could be from blood or saliva or urine, whatever, measuring an analyte or something like that.
But nowadays, you know, people are doing much, much more sophisticated things with LDTs, including detecting proteins and nucleic acids and so on. So even from a technology perspective, never mind the labeling for a moment, even from a technology perspective, the technology of these LDTs is becoming much, much more complicated.
And I'm not suggesting that a laboratory or a hospital doesn't have the technological expertise to manage that, but without any oversight. You know, we talked last time how it's not accurate to say that LDTs are not regulated at all.
They are regulated, but they are not regulated by the FDA. They're regulated under the CLIA requirements, which suffice it to say are not as stringent, not as rigorous as FDA requirements.
And one of the examples I may have mentioned in part, part one is we have, for example, in vitro diagnostics on the market today that are indicated for cancer.
And because they are indicated for cancer, these devices are in fact Class III devices. They require a PMA or maybe an HDE, a humanitarian device exemption.
So, one of the things that I see people, you know, they assume, for example, that something that is non-invasive, in other words, something that does not come in contact with a patient. And remember IVDs and many LDTs, they're not used in the same room. Sometimes they're not even used in the same building as the patient.
That doesn't mean that they're automatically low risk.
If you are using an LDT or an IVD, it really doesn't matter.
For diagnosing a very significant disease like cancer, you have a very significant risk. Not what I call the probability of direct harm because the device is never coming in contact with the patient, but it's what I call my bucket number three, the probability of harm of providing the wrong information, a false positive or false negative.
And this is in fact why, for example, IVDs for cancer are not low risk, they're not moderate risk, they're high risk. They're a Class III.
Like I said, usually PMA or sometimes an HDE. Does that make sense?
Etienne Nichols: It makes total sense. I mean, it. I kind of just do a little bit of a lateral thought here, but it would be almost as if you said, well, which is more dangerous, you know, a pharmaceutical drug or a medical device?
Well, well, what pharmaceutical drug are we talking about? So, you can't really just take that label and say, well, one's safer than the other, one has less risk than the other.
You have to evaluate each one individually.
That being said, I'm curious.
So, I think in our last episode, we also talked a little bit about should LDTs as a whole? And this is getting more into the theoretical, philosophical, what should happen?
Should LDTs be pushed over into the IVD category?
Or is there still some instance where, you know, an LDT makes sense? It is the practice of medicine. And how do we split that hair? Any thoughts?
Mike Drues: Well, great question, Etienne, and I actually have a number of recommendations that I would be happy to share in terms of fixing these problems or at the very least, making, you know, mitigating the risks associated with these problems.
And remember, this LTT debate has been going on for decades.
So, my intention here is not to just simply bash, not to blame FDA or even Congress or hospitals or medical device companies.
The point is what can we do to fix it. So, at the end of our discussion, I have a sort of a laundry list of suggestions. But just coming back to the risk for just one thing, though.
One other thing I wanted to add to that before we move on is to steal a little bit of verbiage from one of FDA's guidance documents about risk.
This happens to be from the wellness device guidance. What they basically say is if a product uses venipuncture, for example, if you have to stick a needle in a patient to obtain blood, and many IV, sorry, many LDTs require a blood sample in order for them to work such a product.
And this is a direct quote from an FDA guidance; such a product is not low risk because it is face.
And one of the reasons, one of the justifications for why such a product is not a wellness device. And I'm kind of using wellness devices as a little bit of a metaphor for an ldt.
I know it's sort of a weak comparison, but a little bit of a metaphor is because if it's a low-risk device, and by the way, wellness devices are not low risk.
They're what I call very low risk. Because a low-risk device is a Class I device,
Class II device is a moderate risk device. And I find it fascinating. I have so many customers, they tell me that their Device is Class II, and then they tell me it's low risk.
It's like, well, how do you connect those dots? Because by definition, a Class II device is not a low risk, it's a moderate risk device. But back to, you know, what I'm trying to point out here is one of the differences between Class I and Class II devices is that Class II devices are subject to what we call special controls.
Class I devices are subject to only general controls. And so the reason why IVDs that require a venipuncture are Class II devices is not so much on the risk of the IVD itself, or in our case, the LDT, but because we would not be able to have controls in place to ensure sterility of the needle and so on and so on if it was only a Class I device.
Does that make sense? And again, for the benefit of our audience, I did a webinar for Greenlight, I think, last year on Class I versus Class II and the difference between general controls and special controls.
So maybe we can put a pointer to that webinar as part of the resources for this podcast as well.
Etienne Nichols: Yeah, taking a note down to do that. Class I versus Class II webinar. Okay, great. Yeah, check the show notes for that. And that should be there.
Yeah, no, that's. That makes a lot of sense what you're saying there. And it's interesting you said the wellness device. Maybe it's not a perfect correlation, but if I were to stack those on top of each other, as far as the regulation goes, I don't think.
I think you're right. An LDT isn't straight one to one comparison for a well-known device, but it's above it in regulation or should be at the very least. So that makes sense.
Mike Drues: It is. And there's a sort of an interesting. We could even go one step further, further, Etienne, in sort of a three-way comparison. A wellness device, which I mentioned already, and I've put out a lot of resources through Greenlight on the wellness device exemption, including a webinar for that that's not regulated by the FDA at all.
So theoretically, if we had a device ready to go this afternoon that was a legitimate wellness device, we could start marketing it here in the United States. We would not need a 510(k) or a De Novo or a VMA.
We would not need a quality management system. We would not need design controls, we would not need FDA registration, we would not need anything.
So, on the bottom of that pyramid, if you will, is the wellness devices.
To use your verbiage, one step, one level above that would be things like an LDT which is still not regulated by the FDA, but it's also not, but it is still regulated at least a little bit by CLIA and then similar to the LDT. I don't know if I mentioned this in our last discussion, editing or not.
Clinical decision support software.
I find it interesting that clinical decision Support software and LDTs are both extremely similar in the sense that FDA does not regulate either one. Why?
Because, and they said this with LDTs as well. They're using their enforcement discretion not to do so.
In other words, and I said this in my podcast with on clinical decision support software, when that will change, when FDA will start regulating clinical decision support software is when companies and the people in them put software out there that quite frankly should not be put out there and causes harm to people and then it starts to show up in the news or there starts to be lawsuits and so on.
That's exactly when clinical decision support software is going to start to be regulated. LDT is very similar. Right now, they're still not being regulated by the FDA in spite of the Theranos fiasco.
But is it going to take another Theranos in order for people to really wake up and pay attention here. I certainly hope not. But unfortunately, that, you know, sometimes happens.
Etienne Nichols: And I remember you mentioning something similar at our last episode. But I want to ask a follow up question to that, and that is, what is.
What is the relationship, or is there a relationship between the LDT situation and Theranos? Did one lead to the other?
Mike Drues: Well, they're certainly interrelated, whether they're cause and effect.
That's an interesting question, but certainly interrelated in the sense that Theranos, let's say, took a fairly liberal interpretation of the definition of an LDT.
In other words, not to get into too much detail, and just as a reminder to our audience, when the Theranos situation sort of exploded several years ago, I was one of many people that were invited to come in and talk about this with FDA as well as other people as well.
Obviously, they push that definition of exactly what an LDT is to its limits, so to speak. Remember, I said earlier, the philosophical intent, if you will, of an LDT is something used, developed, and used in one hospital for use only in that hospital.
But the question becomes, what constitutes a hospital or a clinic? You know, the Mayo Clinic, for example, has multiple buildings.
So, if you develop a LDT in one building of Mayo Clinic, does that mean that they can or cannot use that same LDT in the building across the street?
Mayo Clinic also has buildings in different states. In Minnesota, in Florida, I think, in Arizona, maybe some other places. So, if Mayo Clinic develops an LDT in Minnesota, does that mean that they can or cannot do this in Florida or Arizona or somewhere else?
And finally, what constitutes just from a legal or a business perspective, you know, oftentimes hospitals are owned by companies.
Admittedly, they're usually a nonprofit company, but, you know, is that any different than, say, a private or a publicly held company, like a company like Theranos?
So, remember, Etienne, and I've said this before, many times, you'll probably get tired of me hearing it again in the future.
Regulation is about two things. It's about knowing the words, you know, reading the words of the regulation, interpreting the regulation, and then your ability to defend your interpretation.
So, long story short, I think Theranos took a fairly liberal interpretation of the words surrounding the LDT. That's exactly why, long story short, although they got into a lot of trouble on the. On the quality side for falsification of data and all these other kinds of things, and let me be absolutely crystal clear, there's no excuse in any universe why that should happen.
But on the regulatory side, they really did not get into much trouble other than simply a slap on the wrist, because on the regulatory side, it's much more, shall we say, wishy washy or certainly undefined.
Etienne Nichols: You mentioned so. Yeah, and I have a question about that. So it makes sense to me why I personally, as a consumer, would hope that they would go the IVD route because I know it's a more stringent route.
They would have more risk management activities associated with that route.
But you mentioned that you had a client that was using or. Or considering both LDT and IVD, even though your strong recommendation was IVD. And so, they were still trying to determine that.
But in my mind, until LDT is not a legal option, what are the principles that we should be using that do suggest LDT over.
Over an LDT route? Any thoughts there?
Mike Drues: Yeah, yeah. Well, first of all, we have to be a little careful with our terminology at the end, because I don't want to imply that the LDT is not a legal option, as you just phrased it.
It clearly is a legal option. There are a lot of companies, a lot of labs that are doing exactly this, whether it should be legal or not.
That's a different discussion. And that's part of the reason why we're having this discussion and these podcasts today in terms of why they would prefer the LDT route. In the interest of full disclosure, I have several customers that are working on, let me just say, technologies that could be either IVDs.
Well, they are IVDs, there's no question about it. But they could in some universes also be considered LDTs, because one of the things we talked about last time was from a technology perspective, I gave you examples of devices that were LDTs and IVDs, and yet they did the same thing, they work the same way, and so on and so on.
So clearly, from the company's perspective, just like the hospitals, they would like to avoid the burden, if you will, of having to go through the FDA because it is time consuming, it is expensive. But at the end of the day, Etienne, there's one thing to remember, and that is a test that presents any test, any. Whether you call it an IVD or LDT or whatever it is, a test presents the same risk for patients, regardless of whether it's developed by a manufacturer, in other words, a company, or by a laboratory that is a hospital.
So, I understand from an administrative perspective, from a paperwork perspective, that some people might argue that having to take a product, any product, whether it's an LDT or Anything else through the FDA is going to be more burdensome.
That's a paperwork burden; that's an administrative burden. At the end of the day, the underlining safety and efficacy, in other words, the biology and the engineering, that's what's most important.
And just like this is very similar to the decision that a lot of companies have to make, if they have a device on the market right now under a 510(k) and they want to make a change to that 510(k), do they notify the FDA in the form of a special 510(k) or do they not notify the FDA in the form of a letter to file? A lot of companies will choose the LTF option for no other reason than they think that it's less burdensome, that it's quicker, that it's easier.
In other words, I hate to say it, Etienne, and but it's an excuse to take shortcuts.
And whether you do something as a letter to file or a special 510(k), whether you have a technology, an in vitro diagnostic that's an LDT or a regulated medical device, at the end of the day, the biology and the engineering is the most important and that should be the same.
So, long story short, I think it's a little bit of an oversimplification to simply say that LDTs should not have to go through the regulatory process because it's just, you know, a higher regulatory burden.
Etienne Nichols: And I a hundred percent agree with you. So, the thing that I guess if I were to summarize a little bit about what you said is the same amount of work should be done from a, like you said, a biological and engineering standpoint.
And in this case, it's a matter of getting the credit, really.
So, if you're going to do both of those, why would you not get the credit?
Second thing in my mind is that could also potentially safeguard you when the law changes. And I want to get your thought on this when we do finally have that valid act that goes through.
Because, you know, if it sounds like, especially since the Theranos case is blown up, so to speak, maybe it will take another Theranos case, I don't know. The speculation, at some point it is, it seems like this is going to happen. If so, what. What should companies be doing right now?
Mike Drues: Great question. And so, let's make this, you know, in the last several minutes of this discussion, you know, very positive, very proactive. What can we do now?
Etienne Nichols: Absolutely.
Mike Drues: Improve the status quo and make the world a better place. Because like I said, There's. I don't want to play the lame game here. There's way too much of that.
So, it's interesting. I just used that 510(k) metaphor. You know, a special 510(k) versus a letter to file. I give exactly the same advice to my VD companies now, and yet not even substantially equivalent to use another regulatory fund, but exactly the same advice.
And that is make sure that you have a justification in place. If you're choosing, for example, to take advantage of the LDT loophole, which is very similar to what some people describe as the 510(k) loophole.
If you're choosing to take advantage of that, at least for right now, put together an LDT justification document, just like I recommend to my companies with the letter to file. In other words, here's the LDT that were developed, here's why we're developing it.
And by the way, Etienne, in one of the questions you asked me a moment ago, which I sort of put off, but we can get to it in a moment.
What can we do to. To change the.
This to make it better?
One of the things that I think we should think about is maybe one of the requirements for an LDT is if there is a truly unmet clinical need.
In other words, one of the things I mentioned last time is one of the reasons why hospitals develop LDTs sometime is because there's not a suitable task already on the market.
And so, okay, fine. If there's not a suitable test on the market, then as part of your justification, the hospital or the clinic or the company or whoever's developing this should say, well, one of the reasons why we're developing this is because we have patients that we need to measure XYZ in.
And for whatever reasons, this is not commercially available.
Maybe it's a genetic test that only affects a small number of patients, and it's not worth it for a regular commercial company to develop a test like that because they would only sell a few of them a year, something like that.
So that could be, you know, one of the requirements that we put in there for somebody that wants to develop an LDT. But most important, like the letter to file, I don't want people to see this as a shortcut, as an excuse to not do the things that from a biology and an engineering perspective, remember, Etienne, and my background is in biomedical engineering.
That's what my PhD is in. So, I'm a biomedical engineer first and a regulatory consultant second.
And that's the order that we should think about these things. But unfortunately, not everybody seems to think that way.
Etienne Nichols: Yeah, that makes sense, and I think that's a great way to look at it because a justification document would like I said, give you that credit if and when the time comes.
So that makes sense. I love the practical application there. I am curious though because I really, I'm always curious about the forward looking thing, you know, so if and when the law changes. I have not read the valid act. I started to, I wasn't able to finish it as long as I was expecting.
Mike Drues: Why would that be a surprise, you know, something coming out of Washington D.C. it's not. Well, don't get me started on that.
Etienne Nichols: Occasionally, you know, you luck out. But. Okay, well what are your suggestions though? You know, aside from, from maybe that. But what are your suggestions for improving the status quo? What, what can we do?
Mike Drues: Well, here's another suggestion that I give to my customers even right now, and that is have a contingency plan.
If you have a product already out there under the LDT or you're considering putting a product out there as an LDT, fine. You know, that's, that's something that you still can do.
It's not illegal. And you know, one of the, one of the push pieces of pushback that I get my customers, I just got this from one of my customers a week or two ago.
Well, everybody else is doing it, therefore why can't we do it? You know, I, you know, that's a hard argument from a business perspective to refute. Right. So, you have to have a contingency plan if and when the LDT situation changes.
And whether that's going to be in a month or a year or never, I don't know.
But similar to, you know, the clinical decision support software, that could change in a, in a nanosecond as well.
Have a contingency plan. It's exactly like, you know, I used the letter to file metaphor earlier. I'm going to use another metaphor and that is the emergency use authorization, the EUA that now a lot of companies have products onto the, on the market for Covid as an EUA. Well, one of the first things that I said about the EUA very back in the way, beginning of COVID long before anybody was talking about this stuff, is that this is a temporary authorization.
As soon as the Secretary of Health and Human Services declares that this health care emergency to be over, all of these EUAs are going to time out, they're all going to go away.
So, if you want to keep your product on the market and you don't already have a 510(k) or De Novo or PMA or something for that, you better darn well start working on one.
Otherwise, you're going to have to take it off. As soon as the EUA comes, follow that same regulatory logic for the, for the LDT, the lab, the developed test. Yeah, thank you. The laboratory developed tests. If and when that changes, have a contingency plan, maybe make a plan to go to the FDA with a 510(k) or De Novo or PMA or whatever it is.
I'm sure that if Congress does change the law, just like the EUA, they will give some transition period, some grace period, if you will. In the case of the EUA, looking like it's going to be about six months.
In the case of LDTs, I suspect it's probably going to be six months, maybe even longer, maybe even a year, you know, maybe even with, you know, look at what's happening with the transition of the regulation in the EU.
It's taking, you know, years and years if it's, they're extending it, but, but have a, you know, a contingency plan, a backup plan so that you don't have to pull that product off the market.
Or at the very least you're not like running around like a chicken with your head cut off at the last minute.
Oh my God, you know, now we got to do all these additional things. As a matter of fact, and this is the same thing that I same advice that I give to my EU colleagues with all this quote unquote, new regulation coming into the EU.
And by the way, I don't think anything there is really new, there's a lot of new paperwork, but there's not a lot of substance that, you know, you shouldn't have to be running around collecting new data because as we talked about before, the biology and the engineering is exactly the same.
So that's another very pragmatic recommendation, I think. Does that make sense?
Etienne Nichols: It's something I've always liked about the advice that you give in that, you know, you, you should be able to develop a medical device if you're going to do it consciously.
There are those three things we talked about last time, if I remember, if I can remember them. You do have an ethical obligation. You have a business obligation because money is the air and breathe the air that companies breathe.
But then you also have a regulatory obligation.
But you should be able to do that biomedical engineering and develop a test or develop a, you know, in this case, a test, but a medical device and then when you take it to the regulatory, you know, I think about what the regulatory.
What is it even.
It is something that we have decided is the standard for that that should bring about safe and effective medical devices. And if you're doing that, you should, to a certain degree at least, you should be meeting those anyway, because, you know, safe and effective is safe and effective.
Mike Drues: Well, I couldn't agree with you more, Etienne, and I couldn't agree with you more. You know, as a matter of fact, if you want to get even a little bit more philosophical and take it one, one step further, it sort of begs the question.
And if companies and the people in them, I mean, you know, our audience here, if we did what we knew that we should do, would we even need an FDA?
Would we need, you know, any kind of a, you know, police telling us to do things that at the end of the day, these are things that we should do, and we should know that we should do.
And to be honest, and some people are going to probably think this is very harsh, but if you don't know what you should do from a biology and an engineering perspective, then maybe you're in the wrong business.
I mean, again, I don't mean to be overly harsh, but I take, you know, professional responsibility very, very seriously. You know, a surgeon is responsible for his or her actions.
He or she is responsible for knowing what to do and what not to do and how to do it and. And so on and so on. I think we should be held to that same level.
But unfortunately, at the end, I didn't fall off the turnip truck yesterday. The real world is not always quite so simple.
Etienne Nichols: Yeah, well, no, I appreciate that insight, though, and I think it is valuable and very timely as well. Curious. What else is important? Did we cover everything with LDTs?
I'm sure there are certain things we've missed, but is there anything else that you think is important to share with the audience?
Mike Drues: Yeah, so just a few more suggestions in terms of what the criteria should be for a legitimate LDT, at least, you know, in my opinion, and again, in my albeit naive way, to improve the world and make the world a better place, or at least the medical device portion of our universe.
There should be some more specific parameters defining what an LDT is. For example, in addressing the big three, using the wellness as a metaphor, labeling technology and risk.
On the labeling side, an LDT should not be intended to prevent, diagnose, or treat a disease, injury or condition.
If it does now, you are clearly a regulated medical device. And in that Case, it's going to be difficult to continue to justify. An LDT is not a regulated medical device.
Exactly like I've used this comparison a couple of times now. Clinical decision support software.
FDA came out and flat out said, I don't have a direct quote in front of me that I'm paraphrasing, but I'm 100% sure on the meaning of this. They flat out said that clinical decision support software is a medical device.
Is it fits the CFR definition of a medical device. However, at this time, we are using our enforcement discretion to not regulate them. And basically, enforcement discretion is one of my many favorite legal buzz phrases. All it means is we're choosing not to take a close look at this right now.
However, we reserve the right to change our minds, you know, at some point in the future.
So, we have to put some limitations there on the labeling. If we have LDTs, for example, that are intended to diagnose cancer, then why the heck would any company develop a IVD that's going to be a Class III PMA when they can put the product out on the market as an LDT to do the same thing?
We don't have people doing that yet, as far as I know, but I see that possibility happening.
On the technology side.
The LDTs in the past have been not only well-established technologies, but relatively simple technologies.
I have some companies that I'm working with now that are developing IVDs that are very, very new and sophisticated technologies. They are not well established, they've not been around for a long time, they've not been used by other labs.
So, to put a product onto the market without any serious FDA oversight for a technology that is not well established, that again, sets up a dangerous precedent.
And finally, you know, we talked a little bit about risk.
You know, what specifically are going to be the risk requirements for an LDT? In the past, they have been relatively low risk things.
But if we have, you know, LDTs that are intended to diagnose specific diseases, especially significant diseases, hypertension, diabetes, Parkinson's, Alzheimer's, even cancer.
Now it's going to be hard to argue that these things are still, you know, low or, you know, low risk kinds of products.
So, all of that is sort of on the regular side. A couple of other quick suggestions and then feel free to chime in if you want, Etienne, and we can kind of wrap this up.
If it is truly overly burdensome for a hospital to develop an LDT and have to take it through the, through the FDA, then how about a compromise? How about Requiring a hospital to put their LDT through an institutional review board, an IRB.
Why not? This is something that we do with clinical trials anyway. You can't do a clinical trial without going through an IRB first.
In many cases, assuming that you're not talking about a commercial IRB, the IRB already exists within that hospital or within that, that clinic or wherever it is. So, they have the mechanism in place, some kind of oversight beyond just what the people in that particular lab are doing. You know, if it's not the FDA, if it's not clear so much, how about the IRB I mentioned earlier, you know, having a justification, an LDT justification document, kind of like a letter to file where you document.
Here's why we developed this, this LDT, here's how it works, here's our risk analysis, here's a demonstration that similar, sorry, similar products don't already exist. And so on, you know, requiring. I'm not talking about a 300-page PhD dissertation here, but just, you know, a few pages, a CYA, a cover year, you know, what kind of a document.
So that if and when there is a problem in the future, at least we have something to stand on.
Better CLIA oversight. You know, CLIA has oversight of LDTs, but at a pretty minimal level, maybe. I'm not. Even though I'm a regulatory consultant, I'm not a fan of creating new regulation.
As a matter of fact, more often than not I'm a against creating new regulation because in my opinion, we've already got enough regulation, probably too much regulation. But what I am a big fan of, as you know, Erin, is people understanding the regulation that we have, the regulatory logic, as I like to call it, and applying it in different ways. So, the CLIA framework is a good start, but I don't think it's enough.
Just one or two last ones and then we'll wrap this up. I mentioned the comparison to the Emergency Use Authorization, the EUA maybe having an EUA like pathway, in other words, create a new pathway through the FDA, something maybe sort of, I don't know, sort of a hybrid between an EUA and a 510(k) so that it wouldn't be as burdensome to hospitals.
I don't want to give people excuses for not developing technologies because it's too burdensome, because that's not going to help anybody. But on the other hand, we need to have some oversight to make sure they're safe and effective.
So, creating an EUA 510(k) hybrid, if you will, or an EUA De Novo hybrid, if you will, that would apply specifically to these types of in vitro diagnostics we call lab developed tests. That might be something to at least discuss further.
And finally, there's been some discussion over the last few years about creating a ninth center at the FDA, a center for diagnostic products. And in other words, in addition to CDRH, which, which regulates devices, and CDER, which regulates drugs, and CBER, which regulates biologics and so on, we create a ninth center.
The, the newest, the eighth center, the Centers for Tobacco, was created a few years ago during the Obama administration.
Well, there has been some discussion on Capitol Hill and other places about a new center being created at FDA specifically for diagnostics, not just IVDs and LDTs, although that would be part of it, but other diagnostics as well.
As a matter of fact, Etienne, and as a historical note, sometimes people ask me, why are in vitro diagnostics even regulated by CDRH?
Because one could easily argue that they are not a medical device.
Well, to be honest with you, when FDA started regulating medical devices in 1976, the IVDs in vitro diagnostics were put into the CDRH silo, if you will, for no other reason than there was not a better silo to put them in at the time.
I'm not a big fan of creating more regulation. I'm certainly not a big fan of creating more government or even building a new center. Some people in the past have suggested maybe a center for combination products at FDA that's got some worthiness to it, but I'm not a big fan of that.
But in this particular case, maybe a center for diagnostics might be something, at least something that we can have more discussion on. The point that I'm trying to make here is I don't want to be, you know, just a naysayer.
I'm not trying to talk about all the bad things. On the contrary, I'm trying to make some very specific suggestions to throw it out there so that folks in our audience and our industry can, can think about these things and talk about these things and figure out which ones make sense, and which ones are like, oh, my God, I don't know what this wackadoodle Drew's guys is smoking. He must be smoking his socks. But these are all things that, that I think are worthy of discussion.
I'm sure there are other things that, you know, can be done that you can think of or other people, but those are just some of the suggestions that I would have.
Anything that you would add to that list, Etienne?
Etienne Nichols: Well, just a comment on the 9th center where you would have maybe a diagnostic center just similar to the combination products. The combination is almost obviously there isn't one right now, but it's, it's like a tiebreaker between device versus the drug.
Depending on the PMOA, it seems like it'd be something similar. You, you wouldn't just have to develop an entire CFR part, you know, a 21 CFR for the entire diagnostic.
There'd be a lot of overlap whether it's risk management for sterility and so forth. So, I, I see that being very practical as far as sharing the load for diagnostics because you're removing a lot of that, that, that burden from CDRH.
So that is an interesting idea that I had not, not heard of myself. Maybe it gets my ear to the ground a little bit more, but I like that a lot.
Yeah.
Mike Drues: Just remember at the end of the day, as I said before, and I, and I, and I think it's worthy of, of repeating.
A test presents, whether it's an, whether you call it an in vitro diagnostic or a laboratory developed test or, you know, Shakespeare said a rosemary name still smells as sweet.
A test presents the same risk for patients, regardless of whether it's developed by a particular manufacturer or a company or a laboratory or a hospital or a clinic. At the end of the day, who developed the test, where the test was developed, that really doesn't matter. You know, as a biomedical engineer, I learned a long time ago safety and efficacy of any product is going to be a function of many, many, many, many things.
But one thing it's not ever going to be a function of is who developed it or where they happen to be standing at the time.
That's something that I think we need to remember.
Etienne Nichols: Yeah, I love that you brought out those labeling technology and risk. I think that's important to think about when you're comparing the two. I think that's great.
So, our takeaways for today's episode. I, I thought of a few. One of the things that I go back to the beginning, whether it's last episode or early this episode, when we talk about LDTs, they are regulated by CLIA, but they're not regulated to the same extent with the, with the level of risk that an IVD is and, and it's a false dichotomy to say it's an IVD. LDT versus an IVD, like you said, could be the exact same thing.
I love your suggestions too for companies as far as having a contingency plan and having that LDT justification document. So, I definitely want to reemphasize that. I think that's important for getting the credit for the work you should already be doing.
What are some of the takeaways in your mind that, that, that you know what. You did most of the talking. It's not fair, is it?
Mike Drues: To be honest, I think you just hit the three or four that I think are the most important. So, the fact that you remembered and you were able to identify some of the most important themes, not just in this part two of our conversation, but from part one as well, then maybe I've done a pretty good job in getting my message across.
Etienne Nichols: I hope so. I think it's an important message and it's a good one. Really appreciate it. Thank you so much.
Mike Drues: The most important thing. The most important thing to remember is I don't want any of this to be so burdensome, whether it's to a company or to a hospital that they say, you know what, it's just not worth it for us to do this.
And so, I'm trying to find that compromise, that middle ground, because believe me, I hear it from companies all the time, especially companies that say, as a matter of company policy, we will not develop a medical device that could be or is a Class III PMA.
We want to only develop devices that are Class II or below because. Or similarly they say to their R and D engineers, and maybe as a former R and D engineer myself, this is why makes my blood pressure go up when the company says to the R and D engineers, only make a change to your. To an existing device to the point that we can handle it internally. That is as a letter to file. Do not go beyond that magic point where we would have to notify the FDA either as the form of a special 510(k) or a PMA supplement.
I mean, Ariane, can you think of any better way to hold back innovation than to do things like that? I mean, that, in my opinion, is the antithesis of what regulation is supposed to be about.
So, this is why I'm trying to, you know, not to be, to be the dead horse here, but I'm trying to make as many pragmatic suggestions to find that, that fulcrum, that balance point, that compromise between, you know, enough oversight and zero oversight.
There's a balance point in there somewhere.
We just need to find it.
Etienne Nichols: Yeah, it's. It's like saying, telling an engineer, well, you can use subtractive manufacturing, just for lack of a better word, you can use that. We are not going to use additive manufacturing now make the best product in the world and it's not fair.
It's nice. It's going to stifle innovation 100%. I totally agree Mike. Thank you so much. I really enjoyed the episode. Looking forward to the next time get to chat but I'll let you get back to work.
I know your time is valuable.
All right, thank you so much.
Mike Drues: Thank you everybody. Bye bye.
Etienne Nichols: Take care.
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