Digital Pathology Podcast
Digital Pathology Podcast
111: FDA and LDT's what does it actually mean for the labs? Kitchen chat w/ Dr. Thomas Nifong
What does the FDA jurisdiction for LDTs mean for the labs? Do they need to worry? How do they need to change the way they operate?
In this episode, I talk with Dr. Thomas Nifong, a clinical pathologist and VP of CDX operations at Acrovan Therapeutics, about the recent FDA ruling on laboratory-developed tests (LDTs) issued on May 6th, 2024. We discuss the implications of considering LDTs as medical devices, requiring regulation, and explore the authority of FDA versus CLIA. The conversation also covers historical contexts, practical implications of regulatory changes, and the roles of organizations like CAP, ACLA, and AMP in legal challenges against the FDA. We dive into the differences in requirements between CLIA and FDA, New York's alternative approval route, and potential impacts on lab operations and compliance. Join us for an insightful conversation filled with essential information for those in the field of molecular pathology.
00:00 Introduction and Special Guest Announcement
00:24 FDA's New Rule on Laboratory Developed Tests (LDTs)
01:58 Recording the Podcast: A Casual Lunch Conversation
03:47 Understanding FDA's Authority Over Medical Devices
08:07 Disputes and Legal Challenges
12:03 Practical Implications and Industry Reactions
12:47 Understanding FDA's Focus: Safety and Efficacy
14:11 The Role of CMS and Medical Necessity
14:48 Congressional Involvement and Legal Authority
16:06 Impact on Labs and Future LDTs
18:33 Quality Systems and Compliance
20:16 Modifications and Software Updates
21:16 Conclusion and Next Steps
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Welcome, my digital pathology trailblazers I finally got on the podcast a person that was super difficult to get on the podcast, even though I'm actually very close to that guest. This person is my husband, Dr. Thomas Nifong, And we recorded an episode about FDA and LDTs. So, on May 6th, in 2024, FDA issued the final rule saying that laboratory developed tests, LDTs, are now regulated by the FDA, and they are not LDTs anymore. They are devices, medical devices. And this announcement shook the laboratory space, especially the labs that actually have those LDTs. So, when this was actually issued, I saw my husband advising his company, Acrovan Therapeutics, on how to deal with this new reality. I'm gonna let you know who Dr. Thomas Nyefong actually is, other than he's my husband. But just let me give you a little bit of context because you're basically going to hear our lunch conversation. So I was planning to ask Tom about this problem for a long time because I know he was preparing this for his company. He's an MD clinical pathologist. And he's the VP head of CDX operations at Akrovan Therapeutics currently. So, all things laboratory tests, companion diagnostics. Tests as medical devices and laboratory developed tests. This is what he's been doing for the last 24 years, at least, 10 of them in the hospital systems and 14 in the industry. So I knew he knew, and I knew this was a hot topic. So the plan was to prepare an outline for a podcast where we could sit together and discuss it. So I took out my phone, and as we were eating lunch yesterday, I thought, I'm gonna just record him talking about this problem, This is going to be my outline and then we're going to mic up, sit together. Maybe we can even make a video and do something fun, uh, create this podcast. We finished recording, we finished lunch and I'm asking him, Oh, so when can we actually record for real? And he says, well, we just did record. So clearly he doesn't know too much about podcasting because I would have at least wanted to have. a real microphone instead of my phone, but he knows a lot about the topic, so you're going to just witness our lunch conversation. Straight from our kitchen. You're going to hear utensils. You're going to hear us with mouth half full. So not necessarily studio sound quality, but definitely important content. So here it goes. The conversation between Dr. Thomas Nifong and Dr. Aleksandra Zuraw about what FDA says about laboratory developed tests and what it actually means for laboratories and companies that are creating those tests. And by the way, you might not have known, but you hear my husband in every episode. He's the one actually reading the intro that will follow right now. Learn about the newest digital pathology trends in science and industry. Meet the most interesting people in the niche, and gain insights relevant to your own projects. Here is where pathology meets computer science. You are listening to the Digital Pathology Podcast with your host, Dr. Aleksandr Zhurav.
Dr. Aleks Zuraw:Paying attention.
Dr. Thomas Nifong:Okay. Yeah. Alright. In 2010,
Dr. Aleks Zuraw:there was a guidance,
Dr. Thomas Nifong:so, so, so, FDA, um, indisputably has guided, uh, has, has regulatory authority over. Medical devices. All right. So what then becomes disputable is what is a medical device. And back in the late 2000s, um, certainly in 2010, I know that the FDA, um, published draft guidance where they're basically questioning the, the definition of a laboratory developed test. Now a laboratory developed test. Um, so, so CLIA has regulatory authority over laboratory developed tests. And that was based on, um, uh, you know, the, the CLIA 88, um, which is legislation. Okay. That's law passed by Congress. Um, but. What the FDA claimed in 2010, again, it probably precedes that, but I know that this draft guidance was published in 2010. So they dispute the definition of a laboratory developed test. And they, they claim
Dr. Aleks Zuraw:Who do they dispute it with?
Dr. Thomas Nifong:Well, with CLIA, essentially, and with the laboratory community. They are claiming that, um, a laboratory developed test as initially envisioned. Was a test within a, um, healthcare system where there was an intimate relationship between the, um, ordering physicians and the laboratory. And so it was a way for a lab to create and validate tests, um, that were otherwise not available. And, um, the interpretation and everything was was within sort of a closed environment so that, um, you know, the, the clinicians could consult with the laboratory pathologists, etc. So, what the FDA claims is that these tests that are offered by, um, reference laboratories actually don't fit the definition of a laboratory developed test.
Dr. Aleks Zuraw:That they are a device.
Dr. Thomas Nifong:That they are a device, right. So, so they basically though, came up with a, um, well, well, within their draft guidance, that they claim authority, actually, regulatory authority over all LDTs. So they say that all, all, even going back. Okay. So this is the same thing. This is the same thing over again. It's not new. Well, well, no, because they never
Dr. Aleks Zuraw:executed,
Dr. Thomas Nifong:executed on it. Okay. So they put out draft guidance, but they never put out final guidance on it. This time, so what's new is in 2024, they actually followed through and put out the, um, the, uh, the final guidance, right? And so, you know, from their standpoint, this is, you know, the, this is the law.
Dr. Aleks Zuraw:How binding is a final guidance? Like how legislatively powerful is FDA? They're not. Or are they?
Dr. Thomas Nifong:Uh, well, yeah, they, I mean, so what do you mean? I mean, they can, they can shut down an organization where like force them to close the doors.
Dr. Aleks Zuraw:Okay. But you said CLIA is a law passed by Congress. What in this context is FDA guidance?
Dr. Thomas Nifong:Well, so the, well, so they're basically trying to, you know, get their claim is that they have authority to do this. So if until it goes through the courts, you're not going to know for sure, but at the end of the day, they either have authority or they don't. If they have authority to do this, then yeah, they can come in and shut your door down and stop.
Dr. Aleks Zuraw:Who says they have the court
Dr. Thomas Nifong:That'll go through the courts, right? Until it goes through the courts. It's not completely a done deal. All right. But, but basically there, it, the, the claim comes down to an L that them saying that an LDT, um, is a medical device and is under their authority. And they're saying that that applies to LDTs, even what, you know, the, for the, the purposes of what they're calling an LDT. It includes, um, the, the LDTs that don't meet the original definition of being within a health system. So, things like CX bladder and Oncotype and, and MammaPrint, uh, all, you know, all of these. Um, are as well. Now mammo print actually went through the FDA and got clearance. So they're not an LDT. They are, they're, they're, uh, before, before they ever watched. They're the first, they're the first, laboratory test
Dr. Aleks Zuraw:that went
Dr. Thomas Nifong:through this process. Yeah. Um, As a, uh, as a, uh, de novo, and, um, it, but it was interesting, so, they were, they came out, so mammoprint breast, and the oncotype breast from genomic health. came out similar time frame. Um, so the genomic health launched theirs as an LDT. Mammoprint went through, you know, this whole process. Um, what it, what it shows is that being FDA cleared doesn't help you with either reimbursement or uptake.
Dr. Aleks Zuraw:Oh, really? No. Because the other one is more, uh,
Dr. Thomas Nifong:yeah, well,
Dr. Aleks Zuraw:it's more successful. It was
Dr. Thomas Nifong:more successful partly because Mammoprint initially launched, it was, it was required frozen tissue. Took him many many years to translate it to FFPE. So it was an it was non standard
Dr. Aleks Zuraw:In the nitrogen and stuff Well, or ice? Dry ice. No. Dry
Dr. Thomas Nifong:ice. But no, it's not always sending it, it's obtaining it.
Dr. Aleks Zuraw:Oh, okay. You know,
Dr. Thomas Nifong:it's already FFPE. You can use archive tissue. Mm-Hmm. And this would require, you know, planning it in advance, so, so the, so the argument comes down and you know, the, there, there's a prac. There are a lot of practical elements.
Dr. Aleks Zuraw:Mm-Hmm.
Dr. Thomas Nifong:But whether they really have authority or not is going to come down to a matter of law. And so. That's what, um, CAP along with ACLA, um, and another organization as well, I don't recall, but three, three big ones, um, are, you know, very recently filed suit.
The third one is Association of Molecular Pathology, AMP.
Dr. Thomas Nifong:And so, you know, the, the claim. I have to look through it, I sent you the link from CAP as well, but you know, the claim comes down to a lack of authority of the FDA to do this, and the courts will sort that out. But the, you know, the practical implications are many. One is that the FDA, um, doesn't have the resources to do this, okay? So, there's a lot of, um, Uh, you know, so there, so there, there becomes a long, um, phase in period for this, for one thing. Um, then there also becomes, they're using New York as a, as an alternate route. So if you're New York approved, then you're automatically going to be approved by the FDA. Well, cause the, cause New York is strict and they actually, so the difference, CLIA, CLIA only looks really at analytical. Aspects. All right. It doesn't look at utility. Okay. And, and, um, at, at the clinical utility. And so
Dr. Aleks Zuraw:medical necessity, or that's a different one.
Dr. Thomas Nifong:Medical necessity is not required for FDA. Okay. FDA has two things. Safety, efficacy.
Dr. Aleks Zuraw:Mm-Hmm.
Dr. Thomas Nifong:Alright. Um, cap. I mean, they're looking at safety in the sense that they're looking at the, you know, demonstrate the sensitivity and specificity of the test, but they're not really looking at efficacy per se.
Dr. Aleks Zuraw:So you can have like a useless test, but if it has good performance, then that's fine.
Dr. Thomas Nifong:Yeah. Yeah, so you look at, at, um, the CX bladder test for, for example, you could, you know, if this, um, was all, if this is all done under design control, um, and, you know, you have all of the appropriate, you know, validation studies are done, it could certainly go through and get FDA approval. Uh, cleared. Um, now, does it have utility? Then that becomes whether you get paid or not.
Dr. Aleks Zuraw:Then
Dr. Thomas Nifong:that's a CMS thing. Now, Novitas, if you were FDA approved, I think Novitas was going to use that as
Dr. Aleks Zuraw:Proxy for giving you money? As a proxy,
Dr. Thomas Nifong:yeah. Um, but, but certainly the guy that, you know, even if not, then Indirectly, so the guidelines would take that into consideration.
Dr. Aleks Zuraw:Which guidelines, CMS?
Dr. Thomas Nifong:No, no, no, like NCCN guidelines for, you know, cancer.
Dr. Aleks Zuraw:Okay, interesting. Okay, so, before they sued, there was another, um, like, announcement that they wrote to Congress, either CAP or, who wrote to Congress about this whole ordeal? Okay.
Dr. Thomas Nifong:No, that was,
Dr. Aleks Zuraw:no, there was something that you said that didn't have any bearing. I sent that one
Dr. Thomas Nifong:too. Um, so that was a, a, um, a committee in Congress, basically. I don't know what to call, let, let me say they wrote a memo. Mm-Hmm. Okay. I don't, I don't know what it technically is. I'd have to look back. But they basically. you know, wrote a memo saying that the FDA doesn't have authority to do this, but, but that the committee doesn't have authority to tell them to cease it, to sit, you know, to, to stand down on doing this.
Dr. Aleks Zuraw:Why did they decide now that they're going to follow through? Like, what's their rationale for thinking that?
Dr. Thomas Nifong:Oh, power grab.
Dr. Aleks Zuraw:Okay.
Dr. Thomas Nifong:Don't know. Why would you be motivated? I wouldn't be motivated to
Dr. Aleks Zuraw:I would admit, have more work than I already have. They don't seem to be the fastest, um, organization. Um, another question. But now, until it gets solved, does it mean anything for the labs? For the LDTs? For the future LDTs? I don't know. Well, I think you have to,
Dr. Thomas Nifong:I think you have to operate under the assumption that it's the law of the land until, until, um, you know, somebody gets them to, to withdraw it. Yeah.
Dr. Aleks Zuraw:Oh. So that it is the law of the land. Yeah. Yeah.
Dr. Thomas Nifong:Yeah. I think you would have, I mean, that's how I would interpret it. If I was, if I'm running a, a diagnostic. I'm going to take this into consideration.
Dr. Aleks Zuraw:What about if you, so if you are developing a new one that's Yeah. Like, that's logical.
Dr. Thomas Nifong:Yeah. Well, the old one. What if you're the old ones too? So they, they made some things simpler than what they, uh, you know, had in the approval process in 2010 to make it. a little bit more practical. So one, in order to decrease the burden, they're, um, down classifying, like, like CDX, like CDXs are getting down classified to de novo., so CDXs are getting down classified. but basically what that would mean is, if you We're wanted to create a new PDL 1. You don't have to do a clinical study to do it. You can just compare test to test so you can do positives to negatives if it's if it's a class two, then you can do a 510k against it, but there's still some questions, I'm not the regulatory expert on this, but But the way a 510k works is you're basically comparing it to
Dr. Aleks Zuraw:Something
Dr. Thomas Nifong:another 510k. Yeah, there's a predicate but but but the predicate can't be a PMA there's there's some trickery in in this as well. I don't know. I don't think you can do a 510K directly against something that was approved by, by a PMA. And then there's a long phase in period, too.
Dr. Aleks Zuraw:That's how long? What do they say?
Dr. Thomas Nifong:Five years, I think.
Dr. Aleks Zuraw:So then everybody who has an LDT Then we'll have to register, register it at some point. Yeah. But the, the compliance comes down to, um, some modifications of the quality system to make sure it's compliant. In the lab? Or how do you modify?
Dr. Thomas Nifong:In the lab.
Dr. Aleks Zuraw:So, um, in which, like, how? Are you going to be checking those tests differently so that they comply with being a device?
Dr. Thomas Nifong:It's the, it's the system, yeah, the system requirements themselves.
Dr. Aleks Zuraw:What system? Quality system? The quality system. What is an example of a quality system? Is it the software? Is it the SOP?
Dr. Thomas Nifong:It could be, yeah, so how you, so you have your document, all of your documents controlled. Uh huh You have, um, you know, your, your system for your non-Conformances for your CAPAs. Oh, okay. I think most of the, you know, training and all of that is, isn't any different. That's already captured in, in CLIA and cap.
Dr. Aleks Zuraw:Okay. So you'll have to just add stuff to it so that the, the tests are then compliant.
Dr. Thomas Nifong:Yeah. Alright. But it, but it, it is, and, and they, the the other thing, um, they are making it easier. So, so if you have something that is an FDA cleared test.
Dr. Aleks Zuraw:Mm-Hmm.
Dr. Thomas Nifong:um, you cannot make a modification to it all right? Mm-Hmm mm-Hmm. if you do it essentially becomes an LDT. Okay? But part of what the. And so if you had something that's actually approved, like a companion diagnostic, you'd have to submit another PMA. So how does it work with software as a medical
Dr. Aleks Zuraw:device? You have software updates all the time. How do you, like, you don't go to FDA with every update, or how do you do it? Yeah, yeah, if you
Dr. Thomas Nifong:had a, if, if you have, if, if, so, If you have a companion diagnostic, for example, that includes software, if you made a change, I think you have to submit a supplemental PMA. So it's a big deal. But now with the, they've made that process easier to make modifications. To test, and there may be minor, you know, minor and major criteria. I'm not 100 percent sure how that works, but it's, they did simplify that.
Dr. Aleks Zuraw:Okay.
Thank you so much for joining us for lunch. That means you're a true digital pathology trailblazer. Let me know, I'm gonna post this on LinkedIn, the, probably the full length, uh, if anybody wants to listen straight from there. But let me know in the comments or per email if you would like us to discuss some more on different topics. You can suggest the topics. Uh, basically next time we talk about anything digital pathology related, I will have my mics, my portable mics prepared. And we're going to be ready to roll if you guys want it. So definitely let me know and I talk to you in the next episode.