In this episode, host Etienne Nichols and Shannon Bennett, a regulatory affairs expert in the diagnostic testing space dive into the FDA's proposed rules for Laboratory Developed Tests (LDTs) and In Vitro Diagnostic products (IVDs).
Shannon breaks down the past and present regulatory landscapes of LDTs, the differences between IVDs and LDTs, and what the FDA's changes could mean. They discuss the cost implications and the learning curve for labs new to FDA's processes.
Shannon explains the FDA's four-year phased plan for labs to comply with the new rules, touching on the challenges at each phase, like the administrative burden and the influx of submissions the FDA might have to review. Focusing on the transition for new or modified tests, Shannon emphasizes the need for more guidance from the FDA and educational efforts to help labs understand the new terms and requirements. We also discuss the potential disruption to healthcare and urge labs to actively comment on the draft regulations to the FDA.
Through engaging dialogue, this episode is a deep dive into the regulatory shifts in the lab industry, making it a great listen for those in the regulatory and healthcare fields.
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Some of the highlights of this episode include:
- Concerns regarding the handling of new or modified tests during the four-year phase-in period, emphasizing the need for clear guidance alongside historical tests.
- Discussion on a unique approach from the Valid Act called technology certification, aimed at easing submission and review burdens on both labs and the FDA.
- The significant educational effort required from the FDA to help labs navigate new terminologies and requirements.
- The potentially disruptive impact on healthcare, given the critical role laboratory testing plays.
- Encouragement for labs to actively provide comments on draft regulations to the FDA, advocating for a balanced approach to regulatory developments.
- Year One: The focus is on adverse event reporting, with Shannon suggesting additional FDA guidance to manage irrelevant adverse event reports.
- Year Two: registration and listing phase is discussed, pointing out the clerical burden on labs despite having most required information.
- Year Three: The introduction of Quality System Regulation (QSR) or Good Manufacturing Practice (GMP) requirements in year three is explored, with Shannon mentioning some overlap with existing CLIA compliant quality systems but highlighting FDA's additional documentation expectations.
- Year 3.5 & 4: Shannon delves into the submission of Premarket Approval Applications (PMAs) for high risk, low, and moderate risk tests in year three and a half and year four, underlining the challenge for labs in categorizing their tests and for the FDA in handling a potential influx of 80,000 to 100,000 new submissions.
Links:
- Shannon Bennett on LinkedIn
- IVDs and LDTs: What’s the Difference?
- FDA Proposes New Rule to Regulate LDTs as IVDs: Here’s What’s at Stake
- GG Academy - use Promo Code "podcast25" for a 25% discount
- Greenlight Guru
- Etienne Nichols LinkedIn
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Memorable quote:
"I think the bottom line is this will be potentially very disruptive to the healthcare environment. Lab developed tests. There are studies that have shown that 70% of the information in the medical record is due to laboratory testing. So obviously, they play a really important role in the healthcare environment." - Shannon Bennett
Transcript
Etienne Nichols: Hey everyone. Welcome back to the Global Medical Device Podcast. This is Etienne Nichols, your host for today's episode. Today we're going to be talking about a proposed ruling. On October 3, the FDA published a proposed rule to amend its regulations to make explicit that in vitro diagnostic products, or IVDs, are going to be devices under the Federal Food, Drug and Cosmetic Act. And so that also includes when the manufacturer of the IVD is a laboratory.
And included in this proposed rule, which we'll get a little bit more detail in just a minute but is the idea that they're going to phase out the FDA's historical general enforcement discretion approach to laboratory developed tests, or LDTs.
We'll talk a little bit about what the difference are. So today I'm really excited to have with me Shannon Bennett to discuss this topic. He's an experienced leader in regulatory affairs, quality management.
He's actually an ASQ certified Manager of Quality and Organizational Excellence and an instructor of Laboratory medicine and Pathology. So, before we get into how we met, but just want to say hey Shannon, how are you doing today?
Shannon Bennett: I'm doing well. Really excited to be here. Thank you.
Etienne Nichols: Really excited for you to be here as well. For those of you more longtime listeners, maybe you heard our previous episodes or mine and another gentleman, Mike Dreus. We discussed LDTs in the past and this is actually how Shannon and I met.
He posted an article on LinkedIn, which is a really good article. We'll post a link to that in the show notes kind of the other side or the other take.
And so, I really appreciated the thoughtfulness that you put into this. Obviously, you come from the LDT world and have a vested interest in this. So, love to explore more.
Where do you want to start with this, Shannon?
Shannon Bennett: So, I think just to kind of set the foundation for the conversation and you and Mike talked about this a bit, but I'll just reiterate a little bit. So broadly speaking, there are two types of laboratory tests.
So, you have your in vitro Diagnostic test kit. So, these are made in a factory. There are a couple of vials of chemicals, instructions for use put into a box.
Those companies will develop and validate. Then they need to submit information to the FDA and get clearance or approval. And then they can sell those kits to dozens or hundreds of laboratories around the country.
So IVDs are one type and then the other is your laboratory developed tests. So that is a test that's developed and validated in a single laboratory and then run in that laboratory.
And so historically, FDA has used enforcement discretion, and there are a couple of reasons for that. So, when the medical device amendments passed in the mid-70s, LDTs existed, but they were typically fairly simple, and they were used in support of a hospital population. So, the laboratory attached with the hospital would run tests on that hospital's patients. So, the number of patients affected, should you have an inaccurate test, would be fairly low.
Fast forward to today.
LDTs are quite often cutting edge, so they're much more complex than they were back in the 70s. So, things like next gen sequencing, multiplex mass spec, really state of the art technologies.
And then the other development is today we have large reference laboratories where, again, the test is performed in that one laboratory, however, they get samples from around the country. And so, the number of patients being affected by that test are significantly greater because we're pulling in patients from all over the country.
And so, because of those reasons, FDA has indicated they felt like they needed to act to roll back their enforcement discretion. And the draft regulations that came out on October 3 is not the first go around here.
So back in 2014, FDA published a guidance document discussing here's how we propose regulating LDTs as medical devices. There was a tremendous amount of pushback from the industry.
In addition, there was a presidential election in 2016. I suspect that had a little something to do with it, because we went from a Democratic administration, which tend to be more supportive of regulation, to a Republican administration, which tends to be a little less fond of regulation.
So that may have played into it as well. But ultimately, FDA never finalized that guidance, and so enforcement discretion continued.
The next phase is in 2017; FDA released a white paper discussion paper. Essentially on here are concepts that we think we would use if we were to regulate LDTs. And that eventually turned into a piece of legislation called the Valid Act.
So, the general idea under Valid is that you would put IVD test kits and LDTs under the same regulatory model and would actually create a new product class called an in vitro clinical test, or IVCT.
Now, that's beneficial because today IVDs are medical devices and there's a little bit of a round peg square hole problem there where it's not necessarily a great fit. So IVCTs would be a new class of product that would be a better fit.
The argument would be for IVDs and LDTs. So Valid had two shots at being included with legislation last year being added onto legislation, and in both cases, it was pulled at the last minute.
So valid did not pass.
So, this year, FDA took another look at things. So, they've tried guidance, didn't work. They tried legislation didn't work. So, the other option available to them is Notice and Comment rulemaking. And so that's what we saw on October 3, where essentially, they are now proposing to roll back their enforcement discretion for LDTs and consider them to be medical devices like IVD test kits.
I think the interesting thing is the regulations are several dozen pages, but the actual regulatory change is like a sentence which is LDTs are medical devices now. That's basically it.
And then lots of additional detail.
Etienne Nichols: I have a quick question about this, just because the Valid Act, I know you've seen the different iterations of that, and we're really close with that. What would be the difference in changing the IVDs to the IVCT?
Is that the acronym that they're using? And then I assume putting LDTs under that same IVCT category, is that accurate? And then so what would be the difference had that Valid Act passed versus what they're talking about doing now?
Shannon Bennett: So, I think, broadly speaking, the draft regulations that came out a couple of weeks ago are more restrictive.
And I think that's just the bottom line is they are more restrictive than what Valid kind of envisioned.
Valid in its early iterations were also pretty strict. But over the course of the three or so years that there were negotiations going on between congress, stakeholders, FDA, I do think Valid moved in a more lab friendly direction.
Whereas these regulations that came out on October 3 are, again, a lot stricter and a lot more like kind of the early iteration of Valid or like the 2014 guidance document.
Etienne Nichols: Okay. And different people have expressed different opinions on this. And it's fair if you don't want to express an opinion. I'm just curious, though, if you have a thought, is this the FDA trying to get legislation to move, or do you think this is just the way it's going to be?
I don't know if you have a thought on that or not.
Shannon Bennett: That's a complex political you know, FDA has publicly expressed that they would prefer a legislative approach, but they've also been very clear that since the Valid Act didn't get over the finish line last year, that they feel like they have to go the regulation route.
Etienne Nichols: Yeah, there is a little blurb at the very end that just talks about I'm trying to remember. I think it's Section 13 other issues for consideration. It talks about how the FDA recognizes that there are new bills that potentially could change the legal status of this.
So, they do kind of give that little caveat at the very end there. But okay, we kind of have to move forward with what is happening then. So, what are your thoughts?
You mentioned there's just a very small sentence that really is changing anything. What are the implications for LDT or laboratories who are producing LDTs? What are the implications?
Shannon Bennett: Significant, I think, potentially. And so, FDA goes into that a little bit by their calculations, they have a pretty wide range of what they think it would cost the laboratory industry to move into compliance. But their median value is something like $5.5 billion per year.
So that's a big number. I think the thing to remember is, well, a couple of things.
One, and I think this is a little bit where I commented on the discussion that you, Mike, had, there is this misconception that laboratories are completely unregulated. It's the wild, wild west.
These are people in their garages with instrumentation pumping out test results, and that's just not true.
Laboratories are heavily regulated. So, the primary mechanism for that is a law called CLIA, the Clinical Laboratory Improvement Amendments.
So CLIA is the law that you need to follow if you want to run a clinical laboratory. It's run by CMS. And if you want to run a laboratory, you need to get a CLIA certificate from CMS, and then you're inspected periodically. You need to meet the CLIA requirements, et cetera.
Now, CLIA does focus most of its attention on lab operations. So once the test is up and running, we want to make sure that we have the appropriately trained staff to run those tests.
We want to do proficiency testing to ensure the test remains accurate over time. We need to perform quality control with our test runs, things like that. CLIA does have a section on test validation, but it does focus on analytic validation.
So, one of the concerns that FDA raises is that CLIA doesn't require clinical validity, which is an accurate statement. CLIA does not.
But the thing to make everyone aware of is CLIA is kind of the baseline, the foundation.
There are other accrediting and regulatory organizations that many laboratories work with that have higher standards than CLIA. So, College of American Pathologists is one. New York State Department of Health is another one.
And so those entities do require clinical validity. So, while it's true that some laboratories that are just operating under CLIA may not be assessing clinical validity, a lot of those laboratories that are provided oversight by other entities, like Cap, like New York State, do assess clinical validity. So, I think that's an important thing to bear in mind is it isn't the Wild, Wild West with laboratories.
They are well regulated.
But FDA feels that CLEIO doesn't go far enough when it comes to regulating the design and validation of.
Etienne Nichols: What are. So, I'm thinking, if I were a lab and I'm reading this and I'm trying to understand the other side, maybe I'm not really familiar with IVDs or the process they go through with the FDA to become a marketable test.
What are some of the things that I should be thinking about as a lab? And I don't know if you want to go through the continue to talk about the detrimental sides of this, or should we just talk about whichever direction you want to go?
Yeah.
Shannon Bennett: So, I think the bottom line is most laboratories don't speak FDA. They have had no interactions with FDA whatsoever.
If FDA were to regulate LDTs, the learning curve for your typical laboratory would be very high. So that's first.
And then, of course, there would be significant potentially costs involved, $5.5 billion per year per FDA's estimate. And I think that is because laboratories would need to gather documentation.
FDA does have some different additional requirements for documentation. They'd like to see that laboratories may not have that they would have to generate. You get the submission process itself and then whatever back and forth you have with FDA as you try to get approval for your test.
So, the learning curve for labs is huge.
And I think there are lots of different kinds of laboratories, right? So, you might have a really niche laboratory where they've got like three LDTs, and that's all they do.
And then on the other end of the spectrum, you've got many academic medical centers where they've got a test menu of maybe 1000 lab developed tests. So, the idea of trying to gather submissions for 1000 LDTs in the four-year transition period in the regulations is incredibly daunting.
It would certainly be a very expensive proposition. So, I think many laboratories are going to be faced with a difficult decision-making process of do we want to mess with the FDA at all, or do we shutter our doors?
Or if I'm an AMC, for example, I can't afford to submit a thousand tests to FDA. I can only do 100. So maybe we need to start prioritizing. We're only going to focus on these tests and these other tests we're just going to stop offering.
So, I think there is a legitimate concern about patient access and innovation as well. Again, that's just taking existing tests off the market.
But moving forward, if I'm a laboratory and I've got a really innovative technology that I'd like to develop a test for today, I could bring it up as an know again validate it, high quality test.
But in a future state, if I also have to go through FDA, that might be hoops that I don't care to go through. And so, I won't bring that test up.
And FDA does call that out in the draft regulations. They say something along the lines of, we recognize that some laboratories may opt to take their tests off the market due to resource constraints or whatever the case might be.
And they essentially say, we're comfortable with that because we think the benefit to patients outweighs those tests going off the market. And I think that's going to be a point of significant contention between the lab industry and FDA.
Etienne Nichols: Yeah, because there's no grandfathering in, correct? Yeah.
Shannon Bennett: So valid act had grandfathering. So, what that basically meant is if you had a test on the market prior to X date, it would be grandfathered. So essentially you would not need to retrospectively submit documentation to the FDA, which really helps address some of that administrative clerical burden issue.
The draft regulations don't have grandfathering explicitly. So hypothetically, a laboratory would need to submit every single LDT or at least assess whether they need to submit every single LDT to the FDA.
Now, interestingly, this isn't just draft regulations. It's also a bit of an RFI, because FDA asks some specific questions, and one of them is around grandfathering. So, should we consider grandfathering a subset of tests? What should those tests be? And what evidence can commenters provide that would demonstrate that grandfathering would be okay?
So, they're at least leaving the door open to discussing the possibility of grandfathering in the draft regulations.
Etienne Nichols: Yeah, I was just looking at I hadn't read the comments. Maybe you can speak to some of the comments or some of the bigger comments that have come through. It seemed like there were a lot I want to say upwards of 500 comments came through for this proposed ruling.
I don't know. Have you looked at any of those yet?
Shannon Bennett: I was monitoring.
So, one challenge too, is the fact that, you know, again, FDA did this in 2014. So, if folks are looking at historical comments, just be careful. You're looking at the current 2023 regulations and not the 2014 regulations.
But I do expect there to be many, many comments here.
Certainly, labs are going to comment, professional societies are going to comment, and I imagine individuals will comment as well. So, I expect there to be a significant number of comments to this regulation.
Etienne Nichols: So, one of the things I noticed when I was reading through, I mean, it's kind of early on or somewhere in the proposed ruling, it talks about the different stages,
is what, a four-year rollout of this program, maybe? Before we go into that, I'll just comment on something you'd said previously about the no grandfathering. In previously, I'd heard some people speaking kind of positively about the FDA and how they are sort of learning from EU MDR, the European medical device regulation, and how it has stretched on and on and on because companies are deciding to let their CE marks expire rather than jump through all the hoops that the EMDR is requiring.
And so, this almost seems like a bit of a step in the wrong direction as far as that image. But let's talk a little bit about the stages that they've laid out, though.
Can you speak to some of those?
Shannon Bennett: Sure. So, FDA basically has a four year, what they consider a phase out policy. So, they're phasing out enforcement discretion, which means they're phasing in regulations is another way to think about it.
So, in year one, they are phasing in adverse event reporting. So as a laboratory, if I have an adverse event with one of my LDTs, I would need to submit that in some way to the FDA. So, I think this is a little bit challenging.
So, laboratories have many laboratories I would hazard to guess, probably all laboratories have mechanisms to track adverse events. But the challenge is not all adverse events are created equal. So, for example, if I'm a technologist at the bench and I forget to add one of the chemicals to my setup and the run fails and I have to repeat it, that's an adverse event as far as lab is concerned. But it's not due to a problem with the design of the test. The LDT.
It's human error. Another example is I set a blood tube on a bench. It rolls off rolls underneath the bench, and I don't find it for a couple of days.
It's now outside stability. I have to cancel that test. Nothing to do with the test. Completely human error. I don't imagine FDA wants to hear about those things because again, it has nothing to do with the test itself.
And in addition, that really falls more on the CLIA side of things because it's lab operations I think FDA is primarily concerned with. Do you have any design flaws with your test?
Is your test giving a lot of inaccurate results? Those kinds of things. So, I guess one general comment I have is I think FDA, should these regulations become finalized, will certainly need to develop some additional guidance documents for laboratories to help us frankly understand expectations.
Because again, I don't think they want to get slammed with thousands of adverse events that really have nothing to do with the test itself. So that's year one.
Year two is registration and listing. So, every laboratory that wants to continue performing or developing LDTs would need to register with the FDA and then would need to list information about their test.
So again, most, if not all laboratories have an electronic lab test catalog which will include things like the test name, sample requirements, the methodology used, interpretation, guidance, et cetera. So that's all things that FDA is probably interested in for their listing database. So, labs have that information going off of what was invalid. FDA, I think, may also want some performance characteristics.
So, what's the accuracy of your test, the precision, et cetera. So, labs likely have this information, but it is still a clerical burden to provide all that information to FDA.
But they do provide a year for that to occur. And there are a few other things that occur in year two phasing and labeling requirements.
So, here's an interesting know. An IVT test kit is again a box that I put chemicals into and instructions for use, and then I mail it out to dozens or hundreds of laboratories.
An LDT is a recipe on a piece of paper that I'm going to execute in my lab. There's not a physical thing to move around, right? So labeling requirements as they are, I think, historically understood, don't really apply because I'm not going to slap a label on a piece of paper right.
So again, guidance might be required from FDA on what do they think labeling means in the context of an LDT.
All right, so then we move on to year three, and that is implementation of certain QSR or GMP requirements design controls, document controls, purchasing controls, CAPA. There’re a couple others that they call out specifically. Now, again, there may be a fair bit of overlap with the lab's existing CLIA compliant quality system. So that's positive.
Speaking specifically about design controls, thinking about what are my customers going to want, what does my lab need for this test, et cetera. These are thought processes that labs go through today.
I mean, they think about all these things. We don't necessarily write them down, though.
So, I think that's going to be a bit of a change for laboratories, is just the documentation expectations of FDA are going to be significantly greater than I think labs are used to.
Etienne Nichols: Yeah, that makes sense.
Shannon Bennett: So, I'll pause there. Any questions on the first three years? Because then that's when things get exciting after year three.
Etienne Nichols: Yeah, one quick question. So, you mentioned the accuracy and precision of the test. I've heard IVDs, and I don't know, I'm not as in tune with the IVD and LDT communities as you are. But I have been speaking with some IVD professionals recently, and they talk about the requirements for their accuracy and precision that they feel like it's higher than what an LDT is required.
What is your take on that or your thoughts?
Shannon Bennett: I can't really speak on specifics because every test is going to be different. I can say that every single laboratory is run by an MD or PhD laboratory director. These are people who are very well experienced.
The tests are performed by medical technologists who have CLEIO required educational backgrounds in life sciences or clinical laboratory science. So, there's a lot of expertise in the laboratory. And so, we really rely on our lab directors experience and expertise, certainly as necessary.
We'll reference things like CLSI guidance documents or other guidance as we develop our validation studies. But I think the level of rigor and the level of quality in LDTs is equal with IVDs, broadly speaking.
Etienne Nichols: Okay, the other thing was the QSR or the GMP requirements. I am just personally curious about that, not being as familiar with what CLIA requires. I know that there's going to be some overlap because I know CLIA requires quality system.
What are some of the you already mentioned design controls, but are there any other aspects that may not have overlap that may require additional lift?
Shannon Bennett: So, I think there will be quite a bit of overlap. I think it's a question of degrees. So, like CAPA, for example, a laboratory may do CAPAs in certain circumstances. FDA may expect CAPAs done in other circumstances. So, labs may just need to expand what they do for those purchasing controls. Labs certainly manage their reagents and validating that they knew lots work and tracking and so on and so forth.
Again, FDA may expect slightly different have slightly different requirements or slightly more requirements. So, it's kind of a matter of degree, I think. The Venn diagram of QSR and laboratory quality system, there's a fair bit of overlap there.
But again, there are concepts that labs are not familiar with, at least not by what FDA calls them. Design controls is a great example.
Etienne Nichols: Yeah, it's just kind of interesting too, with the different moving pieces. Right now. If you're familiar with QMSR, the proposed ruling to move from QSR to harmonize it with ISO 1345, for example, the FDA is currently working through how they're going to change the previous Q-SIP, the quality system inspection technique.
So, it’s kind of just raises a flag in my mind. How will they be inspecting these labs? I'm sure that's going to be a completely new way of doing things than maybe they did previously with a manufacturer.
So that's going to be an interesting thing as well. Do you have any comments or thoughts on that?
Shannon Bennett: So as far as the harmonization in the guidance documents, FDA acknowledges the fact that they are currently working on that and basically say, don't worry, we'll have it harmonized by the time you guys have to do it.
So awesome.
As far as inspections know, I'm sure FDA would intend to have an inspection regime. I can say that is one thing labs are a little bit concerned about, because labs typically don't have a development team in a building over there, and a lab runs over here.
Quite often your development staff and your operational testing staff are sitting right next to each other. And so, there's a little bit of concern about scope creep, frankly, with FDA inspections.
For example, will they start looking at things that are really more clear and other way too? Will CLEIO start looking at things that are covered by FDA? And labs are essentially double regulated.
So that is a concern that the lab industry has brought up.
Etienne Nichols: Yeah, okay. Yeah. Stage four, you said things get interesting. What changes?
Shannon Bennett: So, year three and a half, by year three and a half, the expectation is all class three high risk tests should have a PMA submitted by that point, and these are just for existing tests. Now we're talking.
So, I think, again, getting back to guidance documents I think FDA will need to create is helping labs figure out which of their tests are low risk, moderate risk, or high risk.
So again, labs don't necessarily think of tests in that way. All tests are high quality. We want to have mitigating factors for all of our tests to make sure we're getting accurate results, et cetera, et cetera.
So, this low, moderate, high risk might be a little bit of a new concept for some laboratories.
Now, interestingly, FDA notes, maybe learning from the IVDR experience, like you mentioned, that as. Long as you submit your PMA application by that three-and-a-half-year deadline, or if they change it, whatever the deadline happens to be, you can continue running your existing test in parallel with FDA performing their review.
So, it's good. It's also interesting.
One thing that I forgot to mention that provides some very important context here is how many LDTs exist in the wild.
Nobody knows because there's no centralized database.
Etienne Nichols: I almost asked you, but I thought, well, how would he know that, right?
Shannon Bennett: But we can do some extrapolation. So, the Pew Charitable Trust did a study where they determined that they think there are roughly 12,000 laboratories that could be developing LDTs for reasons we don't need to get into.
But 12,000 labs, if you assume an average of ten LDTs per laboratory, we get to 120,000 many laboratories. So, the lab that I currently work for, we have about 1600 LDTs.
The association for Molecular Pathology has estimated there are, I think, between 60 and 100,000 just molecular tests. So, I think it's pretty safe to assume the universe of LDTs is probably in that 100 to 200,000 right now.
Now, FDA does state they feel that about 50% of tests won't need any submission, presumably because they're exempt.
We can quibble over how accurate that number might be, but even if we say 50%, we get down to 80 to 100,000 tests. It's 80 to 100,000 packets that FDA is going to have to review.
So, there's going to be this massive bolus by the end of this transition period of submissions that FDA will need to be reviewing. So that is also an area of, I think, some concern, not just for the lab side, but I have to imagine, for other medical device manufacturers, because FDA has a finite number of submissions they can review for all medical devices. And if you jam 80 to 100,000 new submissions into that pipeline,
it could cause problems for other people.
Etienne Nichols: Yeah, I'm just running through some of the thoughts in my mind where the cost associated, I mean, they're going to have to establish as a manufacturer, I would assume, the submission costs.
There's the additional QSR costs. So that gap analysis. We forget sometimes about just the analysis to determine what's going to be needed and then the actual filling of those gaps.
So, yeah, wow. 80 to 100,000 tests from the FDA side. That's a lot.
I'm curious what they're currently staffed for. I mean, maybe that's something a topic of a different discussion or maybe we can look into that later. But yeah. Okay, stage five.
What are the thoughts there?
Shannon Bennett: Year three and a half is PMAS for your class threes, and then by year four. So, six months later, laboratories would need to submit any low or moderate risk tests. So basically, the remainder of your tests that need to be submitted would need to be submitted by year four.
And again, once you make that submission by the deadline. You can keep that test on the market while FDA does their yeah, okay.
Etienne Nichols: Well, at least that's good.
You mentioned a couple of guidance documents. I tried to take some notes here, one being the level of risk for tests. I don't remember what the first one was. I think it was about the adverse event reporting.
Adverse event reporting? Yeah. Okay. Just going to kind of take some notes.
What are some other things that you think are going to be, I mean, guidance, necessary guidance documents is a really interesting thought that you've kind of brought out to some different ones. Do you have thoughts on others that, you know, the industry is at least going to need to learn about this?
Shannon Bennett: So, I think another open question, that four-year phase in period is for tests currently on the market.
Laboratories are constantly developing new tests and making modifications to existing tests. So, what happens with those on the date that the regulations are finalized?
Do I need to start submitting PMAS and so on for new tests I have coming out to the market?
If there's this bolus of 80 to 100,000 historical tests, what does that do for new tests? Do they go to the end of the line? Do they get prioritized? How does that work?
So, I think some additional guidance on that transition period for new tests or new modifications to LDTs would also be something that hopefully FDA is thinking about.
Etienne Nichols: Yeah, that makes sense.
If we went back to design controls, you mentioned that and just like any good engineer, you think about the process of design controls, but you don't always write it down and the design inputs, design outputs, controversy, or what's the user need versus the design input.
I am seeing that as that would be a difficult thing to really apply in this situation, I suppose.
And I don't know what your experience is with design controls, how much you've dealt with it.
Are there any specific things within that whole process that you see as we may need some guidance regarding this?
Shannon Bennett: Well, I think not even just with design controls, but in general, as I think I mentioned before, but labs don't speak FDA. So, I think there will certainly need to be a significant educational effort on FDA's part to really get labs up to speed.
Labs want to do the right thing. We all want the same thing, which is safe and accurate tests for our patients. But labs may need some help gaining the understanding of all these requirements. And the terminology, terminology is always tough.
So, I think the educational effort is a really important consideration.
Etienne Nichols: Yeah, well, I appreciate you walking me through those. What are the other things missing in this before we switch gears, because I would like to talk about comments you have and things that you would change.
I know you likely have an opinion about that, but anything else we missed, assuming things don't really change regarding the proposed ruling,
I think the one thing.
Shannon Bennett: I'll flag there was a really interesting concept in the Valid Act that isn't in these regulations called technology certification.
I think of it as a center of Excellence approach, where a laboratory could submit a test to FDA using a particular technology, as well as some supporting quality related documentation.
FDA would review that test, let's say it's in mass spec, and would review all that documentation and say, hey, Laboratory X seems to really know what they're doing with mass spec testing. We're going to give them technology certification, meaning they can continue implementing new mass spec tests and modifying mass spec tests and don't need to be making constant submissions.
So that has the dual benefit of reducing the submission burden on the laboratory, which is something that is a major concern, but also reduces the review burden on FDA. They have some assurance that Laboratory X knows what they're doing with that technology and can kind of let them do their thing.
Now, FDA has stated they don't feel that they have the statutory authority today to use such a concept. And so, you don't see something like that in the draft regulations.
But it sure would be nice to try figure out a way to make that Tech Cert or Center of Excellence like approach work, because again, I think it'd really be a win win for both Lab and for FDA.
Etienne Nichols: Yeah, it's almost as if, showing the practice of medicine, we know what we're doing, you don't have to worry about us. That makes sense.
Do you have comments on how that would work specifically? I mean, you said it was in the Valid Act, but any additional details regarding that?
Shannon Bennett: I think valid laid it out pretty well.
Etienne Nichols: Okay, well, if the Valid Act had passed and we were looking at an IVCT for both LDTs and IVDs, obviously it feels like it would take the IVDs a little bit away from the FDA to a certain degree.
But what would that look like regarding the industry and LDTs and IVDs? What would change versus what we're looking.
Shannon Bennett: At right now under a valid construct? Right, so I think it would actually make the IVD manufacturer's lives a little easier, because they'd still be regulated by FDA, of course. But I would argue that the IVCT concept, that new product type, would be more fit for purpose, I guess, for IVDs.
So, I have to imagine there are some things that are a little bit challenging for IVD manufacturers to document or demonstrate today under medical device that would maybe be a little bit easier in a more fit for purpose regulatory construct.
Etienne Nichols: Yeah, that makes sense.
So as far as timing goes, these 60 days after it's published is when it would come into effect, is what they say, but we don't know when it would be published.
Just looking at previous proposed rulings and some of the time that it takes.
I don't know if you have a thought or if you talk to anybody who knows, but I guess at least a year, but I don't know if that's accurate.
Shannon Bennett: Well, I think the thing that cloudies the water is the fact that next year is an election year.
Etienne Nichols: Right.
Shannon Bennett: So, I think FDA is going to be motivated to get it out sooner than later.
There is a 60-day comment period to December 4.
I imagine there's going to be a lot of comments that FDA will have to wade through, so they probably want to get it out quickly, but there are probably going to be a lot of comments to get through, so I really don't know how quickly they're going to be able to turn that around.
Etienne Nichols: Yeah, it'll be interesting to watch. It'd be interesting to see it play out.
What else? Any other thoughts or comments about this? I know you covered a lot of different ground, different aspects, but what other comments do you have?
Shannon Bennett: I think we covered a lot of it. I think the bottom line is this will be potentially very disruptive to the healthcare environment. Lab developed tests. There are studies that have shown that 70% of the information in the medical record is due to laboratory testing.
So obviously they play a really important role in the healthcare environment.
And I think I'm just hopeful that however this plays out, that the disruption to the healthcare industry will be minimized. Because at the end of the day, we want to make sure that patients have access to high quality, accurate tests.
Etienne Nichols: Do you have advice to labs that are experiencing or seeing this for the first time, ways to get ready or something they should be doing? Right now?
Shannon Bennett: I think the first priority is comment. So, again, comments are open till the December 4. I would highly encourage everyone, whether you're a lab or you're another IVD manufacturer, to make your voice heard.
FDA really relies on subject matter experts like all of us to make suggestions and tell them about things that might have unintended consequences or things they're not thinking of. So, I just highly suggest that everyone submit comments to the FDA on these draft regs as far as what can labs do to prepare, it's challenging because you don't want to get too far ahead of where the regulations are, right?
Etienne Nichols: Yeah.
Shannon Bennett: So, I think the bottom line is this is definitely something to pay attention to. It's not a time for panic, but it's a time to keep an eye on what's going on. I guess the other thing I should in fairness, mention that plays into this as well is about 35 seconds after these draft guidances are finalized, I'm sure there's going to be lawsuits involved,
because when you have this big of a change to an industry, somebody is going to sue. So that plays into this as well.
And I raised that because I don't think labs should sit back and think, oh, people are going to sue. This isn't going to happen. I don't need to worry about it. I don't think we can assume that. So, I would strongly recommend that folks read through the regulations, try to get an understanding of what this might mean for them, and then provide comments to FDA.
Etienne Nichols: Yeah, that is tough because you don't want people just ignore it in hopes that it'll go away. Similar with the EMDR type situation, you don't want to hope there'll be an extension.
Okay, that makes sense. So, wow, you brought up an interesting point with the timeline.
If they do want to move quickly, that could be much less than the year. So that'd be interesting.
Very cool. Well, thank you so much for coming on. I really appreciate you going through the proposed ruling. It'll be interesting to watch this. Maybe we'll have to do a follow up episode.
Once the published one comes out, we can talk a little bit more, if that's interesting.
Yeah. Where can people find you if they want to reach out? Is that okay if they reach out to ask direct questions? Any thoughts?
Shannon Bennett: I'm on LinkedIn.
I'm always happy to talk shop. I can't provide regulatory advice or anything, but I'm always happy to talk about what's going on in the regulatory arena, in the diagnostics testing arena.
Etienne Nichols: Okay. We'll put a link in the show notes so that people can find you. And again, thank you so much for coming on the show. We'll let you get back to it.
Thank you so much for listening. If you enjoyed this episode, reach out and let us know either on LinkedIn or I'd personally love to hear from you via email. Check us out if you're interested in learning about our software built for MedTech. Whether it's our document management system, our CAPA management system, the design controls risk management system, or our electronic data capture for clinical investigations, this is software built by MedTech professionals for MedTech professionals. You can check it out at www.Greenlight.Guru or check the show notes for a link. Thanks so much for stopping in. Lastly, please consider leaving us a review on iTunes. It helps others find us. It lets us know how we're doing. We appreciate any comments that you may have. Thank you so much.
Shannon Bennett: Take care.
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The Global Medical Device Podcast powered by Greenlight Guru is where today's brightest minds in the medical device industry go to get their most useful and actionable insider knowledge, direct from some of the world's leading medical device experts and companies.
