Speaking the Language of IVD

In this episode of the Global Medical Device Podcast, host Etienne Nichols delves into the intricate world of in vitro diagnostics (IVDs) with Christie Hughes, a principal consultant and IVD expert at Qserve Group.

With over 25 years of experience, Christie shares her extensive knowledge, discussing the nuances of IVDs, regulatory landscapes, and practical insights for professionals transitioning into or within the IVD sector.

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Key Timestamps

• [00:00:45] - Christie Hughes's introduction and background in IVDs
• [00:03:30] - Discussion on the regulatory challenges and trends in 2023
• [00:15:22] - Differences between IVDs and other medical devices in terms of regulatory and operational frameworks
• [00:25:50] - Impact of regulatory changes on labs and manufacturers
• [00:40:10] - Detailed exploration of user needs and design controls in IVD development
• [00:52:00] - Advice for medical device professionals entering the IVD space

Key Takeaways:

Links:

• FDA decision summaries for recent IVD clearances
• European In Vitro Diagnostic Regulation (IVDR) updates
• CDRH Learn
• FDA Proposed Rule for LDTs
• Episode on LDTs with Shannon Bennett
• Christie Hughes on LinkedIn
• Etienne Nichols on LinkedIn

Memorable quote:

• "Understanding the user—whether a lab technician or a layperson—is critical in IVD development to ensure safety and effectiveness." - Christie Hughes

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This episode is brought to you by Greenlight Guru, a quality management system and electronic data capture software designed specifically for medical device companies. Streamline your processes and stay compliant with Greenlight Guru.

Transcript

Christie Hughes: If you're already a regulatory person, take advantage of the fact that the FDA publishes decision summaries. Go out there and look for, you know, recent IVDs that have been cleared and start reading those decision summaries and just see how different those look. And you'll also see in there the expectations for the studies they have to do.

And you're going to be. Your mind's going to be blown, I promise you, because I know that my mind's blown, that all IVDs have to do a clinical and not all med devices do.

And we're in vitro. That's always blown my mind.

Etienne Nichols: Hey, everyone. Welcome back to the Global Medical Device Podcast. I'm excited to be talking with Christie Hughes today. We're going to be talking about learning to speak the language of IVDs.

And Christie is one of the best people, I think, that we could have on the podcast to have this conversation. I know Christie through the actual course that we teach at raps, the regulatory affairs professional society.

We teach a…we've been doing a workshop for several years, us essentials for regulatory or us regulatory essentials. Correct me, I can't get the title.

Christie Hughes: It's something like that for medical devices. And it's all about, if you're new to trying to get your device on the market with FDA in the US, we're going to get you there.

Etienne Nichols: It's always, it's always been fun getting to interact with people who are at those different stages. But anyway, so I'm excited to have Christie with us. Christie Hughes is a principal consultant and IVD expert with Qserve Group.

She has over 25 years of experience in the in vitro diagnostic medical device industry. And correct me where I get this wrong, but my understand is you have a degree in medical laboratory science and began your career in hospital clinical laboratories, is that right?

Christie Hughes: That's correct.

Etienne Nichols: And I think last time we talked, you were talking about how you are deeply entrenched in the iv. You teach the US FDA regulatory essentials, but lately you've been entrenched in IVDs.

Christie Hughes: Yeah. So, it's all about everyone trying to transition themselves to the regulations for or try to even understand what they mean to them in Europe. So.

Etienne Nichols: Yes.

Well, thank you for being on the podcast with us today. Those of you who are regular listeners, maybe you've been following along some of the things that are happening, and one of those things that are happening, I mean, if I step back and look at the US or even global regulatory landscape, 2023 has been a shifting year. I don't know if other people have felt the seismic activity, but one of those things that is changing is the, the FDA's proposed ruling to treat LDTs as IVDs and to begin, or I guess, to roll back their enforcement discretion when it comes to those LDTs.

So, if you've been listening, maybe you heard a previous episode where we talked to Shannon Bennett who, who comes from the LDT space and has a little bit of experience in IVD, but he was talking about the differences in language, and I thought it would be good to have an IVD professional who comes from, who's seen both sides a little bit as well and maybe talk about the differences and learning to speak that IVD language. Do you want, do you want to kind of start there, Christie?

Christie Hughes: So where do you begin? So, I did listen to that podcast and that was great. Thank you for having that and posting that. It's very important topic right now to discuss.

And I appreciate that. You know, working, having worked in the lab myself, they, they are a very heavily regulated environment and yes, they have different, you know, certain requirements expected of them.

But it's, it's interesting to even listen to Shannon because the, it's just different perspectives. You know that the laboratory is very mindset of, you know, getting the specimens tested accurately, consistently, making sure that they're getting that right result out there.

And that's what they're kept held to with proficiency testing and continued inspections developing the lab test. Know this is kind of a little different space for them. A lot of them have been doing it for a long time, but they're not necessarily the, the same mindset as a manufacturer and not necessarily the same expectations as a manufacturer might be held to.

And I think that's where some of the surprises are going to come into.

And it's not that they're, they're absolutely capable. It's not that at all. It's just, it's just really, it's the mindset. And so, it's, it's going to be, that's, I think, going to be some of the hardest things they face, the language in the text and the terms and things of that sort, as well as just the level of expectations that are going to be put upon them as manufacturers have already gone through. It was interesting, too, to me because the level of burden coming their way and how it's going to be hitting them.

It sounds very familiar with what the manufacturers have already been experiencing going into the new European IMDR regulations. So, it almost sounded like the same story. So maybe FDA needs to take a, take a look and talk to some notified bodies about how it's going over there.

Because over in Europe, a good 80% to 90% of the in vitro diagnostics on the market today are on the market because they were self-certified. So, manufacturers just wrote up technical documentations in accordance with the directive that was out there, and self-proclaimed that they were in compliance with that.

Yes, someone did a very cursory review of that. If they were not in the union already. If you're in the union already, you could just put your own mark on there and register it locally to say, hey, I have this and start putting it on the market.

If you were foreign, you might have to go through a European authorized rep. But that level of review is kind of more like checklist. The elements are here, not necessarily any kind of deep dive into whether or not what they said was true.

So, the eye-opening experience is happening in Europe under the IVDRs is the bar has been significantly raised as to what they expect to see, and there's no grandfathering, so everyone has to come back through.

So, sounding a lot like lVDs, there's lots of those out there as a high-cost burden to transition into that compliance quality system, as well as device performance documentation expectations.

And so, a lot of IVD manufacturers have been going through what he's talking about. The labs will have to go through, and that's kind of looking at your catalog and deciding what's going to stay on the market for me, because that's a lot of money to transition these devices.

I've also got this explicit timeline, which, yes, they've given us a little bit of breathing room, but the problem there is that management cuts budgets when they hear that. And so, it doesn't really help those manufacturers because their management just said, oh, good, you get to wait longer.

Like, no, I need to do this now. But they don't have the money to do it. So, it's interesting case studies that they sound a lot alike. So basically, something's coming big that's changing their world, rocking their world.

They're going to have to learn a lot about something they don't know a lot about. There's not going to be any guidance for them to do it. And that's the shameful part.

Even in Europe, there's still not enough guidance for IVDR and it was published in 2017. It's been very painful. And so, and then, you know, these folks then have to guess their interpretation of that, try to submit to the notifying bodies for review and then get told they didn't interpret it.

Right. Well, thanks. But there was no guidance. What am I supposed to do? And I kind of heard that with Shannon as well. It's like we don't speak FDA, so then what do we, how do we know to do this right?

And so, guidance seems to always come after regulation instead of the other way around. So that's going to be painful for them as well.

Etienne Nichols: And that's, that's a great point. And I hadn't even thought about making that comparison to what the IVD manufacturers are experiencing to that, with that transition from MDD to the EU MDR.

If you have not heard that episode with Shannon, I'll put that in the show notes so that you can go back and listen to that. Maybe that would make more sense to get you up to speed to, to where we are and what we're referring to.

But if we zoom out and we look at this, okay, that, that's a proposed ruling, it may change. Who knows exactly how it's going to change? I mean there are, there's legislation that may come into play.

Who knows exactly what's going to happen there.

Understanding that proposed ruling is pretty close to where you're going to get most likely. All that being said, if we zoom out and just say, okay, well what if we have a medical device professional who wants to come to the IVD world or an LDT professional who wants to come or has to come to an IVD world.

Let's just talk about some of the language around IVDs and just if you’re an in vitro diagnostic professional now, maybe, maybe new to the industry, what are some things that you really are going to have to get up to speed on pretty quickly?

Christie Hughes: It’s a great question. So even just backing up to thinking that, oh, I work in med device, I can go apply to be a regulatory person at this IVD company, well its very different.

So just backing way out, just the definition differences.

So IVDs are a subset of medical devices. So even when you're trying to, let's say, write your technical file for the IVDR, you have to qualify your device. So, you first have to kind of, and even with FDA, the process should be, I look at those definitions and yep, I meet the definition of a medical device, then I go and see, do I also then meet the definition of an in vitro medical device.

And so, the differences there are, you're doing, you're either a reagent, which is chemical or biologic, some kind of liquid, an instrument or even software or some combination of these.

And those are being used to do some kind of diagnosis, monitoring of, to look for maybe some kind of human condition or disease or pathological process going on based on a specimen taken from a human.

So that's kind of the main difference there, because there's medical devices that do diagnosis and monitoring and things of that sort, but they're interacting directly with the human body. So, like radiology, CT scans, MRIs.

So, the main difference in in vitro is that word, in vitro, it's out of the body, it's external to it. We never have to worry about sterilization, which is I'm very thankful for.

So, it's, you know, it's taking the specimen away from the body and then doing that testing on it. So that's kind of what makes us in vitro diagnostics. So, definitions aside, though, the reason we even get our own divisions of review both in, you know, we get our own set of regulations in the EU because we're, the performance characteristics are so very different.

So, the validation and verification of an in vitro and even the design of it is so very different than other medical devices. And that's because, again, they're in vitro. Right? So, it's a very indirect thing. So, when you're doing a test of somebody's specimen, you want to make sure that you're either finding, if it's a quantitative test, you're getting that number right.

If it's a positive negative situation, that you're really getting a positive that's a true positive or negative, that's a true negative. And so, the reason that's different is because to determine whether or not you can do that, the testing required to show that is very different than any other medical device.

So, we end up in our own little niche situation, and we have all of our different own standards of how we have to do that and expectations.

Etienne Nichols: For how we have to show that that makes sense. So, you mentioned something about the difference in the why they get their own department. Maybe we could start there a little bit with FDA and talk about how it's, that the organization is laid out a little bit differently and how you get your own department.

Is that what do you think that might be helpful?

Christie Hughes: I can kind of speak to how it's, how it is organized. I mean, the medical devices are already kind of split out into different specialties, so you've got, I think, what anesthesia and those guys have.

The department radiology now has its own. It was always with IVDs, I guess, because we were both diagnosing.

But then within IVDs, there's even subspecialties. So, you might have blood counts when you get your white count, red count, that's hematology. That's its own specialty. Subspecialty of in vitro.

Your chemistries or clinical chemistries. So, your sodium, potassium, glucose, those are in the chemistry area. If we're talking about any kind of microbe, virus, a bacteria, fungus, those are in microbiology.

There's even another subspecialty that it's super on its own. And that would be histology. So that's the tissue that comes out of your body, maybe during surgery or biopsy, that gets looked at by pathologists on the slide and staining.

And then there's immunology, and I think that's. The other one is immunology. So that's like, the antibodies. You have the antibodies, something that you're looking for. So, there's a lot of different subspecialties in the lab.

And one more, and that's actually under CBER, not CDRH. And that is the biologics of screening for blood. We call it blood banking. That's, you know, do I have, what blood type do I have that testing?

And then whether or not I'm screening blood that's been collected from somebody that's being donated for. For infusion. So those are also in vitro, but because they deal with something being usually infused back into a body or leading to that, then they have their own even super special subgroup in CBER, because they're handled differently, because, again, they kind of relate to something, either getting even an organ transplanted or blood being transfused, or plasma platelets.

Etienne Nichols: So that's really helpful. Especially me being, again, I'm probably the beginning. I am the beginner, for sure, because I've not worked with IVDs as a medical device professional. So that's very helpful for me when I also think, okay, what about the pathways to market?

Because that may be a good starting place, too, for, like, a beginner like myself. You know, if you. I'm used to class three, class two, class one, based on risk, how does that translate over to IVDs?

Christie Hughes: So, we still have class one, two, three, of course, because that's just the structure of the FDA.

The high risk, low risk comes down into how the test is used. Everything's down to your intended use. In Europe, they call that the intended purpose. It's the same thing.

And that's just, that comes down to what does the person that's making this device intend for it to do? So, when I say intend, that comes down to what you state in something called an intended use statement.

But, you know, in the last ten to 15 years, FDA is also coming around to what you put on your website, what you do in your marketing, what you say at a trade show, all those things show intent.

So, you know, that allows a manufacturer to try to put some limits around how they want their product used.

Now, I've already lost my trail of where I was going with this, but.

Etienne Nichols: No, no, no, that's okay. Yeah. Just different levels of risk as far as. Well, if.

Christie Hughes: So, if you think about how tests are usually used, you go into the doctor's office, you present with symptoms, you're like, oh, this hurts, or feel achy. The doctor's trying to examine you.

So, you know, they're interviewing you and getting your history, they're getting your physical information, they're taking your blood pressure, listening to your heart. They're maybe you're enslaved. And they see that they're palpitating.

And then to start to rule in, rule out things, they start ordering tests. Some of those might be radiological, and some of those might come down to an in vitro diagnostic test.

Lab test. I'm going to send you over to the lab. You're going to have to go pee in a cup, go get your blood drawn, five different color tubes, and then we'll get back to you.

And so most in vitro diagnostics fall under, you know, we have a class one, two, three class ones being exempt. There’re some things that fall into that, but it's going to be kind of really more older technology, like a plate used for microbial culture or, you know, slides and staining that might be used for tissues, things of that sort. For the most part, in vitro fall into a class two. There are some class threes, and the differences, I would say there, the things that mostly fall in the class three for an in future diagnostic would be a companion diagnostic is always considered a class three at this point.

I think there have been some recent guidances and, or I'm forgetting the right word for it, provisions for certain companion diagnostics, because there's so many now, they allow some of those to now be class two, but just.

Etienne Nichols: Oh, sorry, just for definition. So, companion diagnostic just basically, I am going to give someone a drug and I want to make sure it's reacting so maybe I'm going to give them more.

And this companion diagnostic is telling me how it's interacting on a very high level.

Christie Hughes: That's one use of it. So, companion diagnostic means a diagnostic used in companion with a drug that could be used to decide whether or not the drug is a good candidate for you because usually it's based on a genetic marker.

It could be decided to not give it to you because maybe you won't metabolize that drug. Well, so it's a waste to even give you that drug and it can also be used for monitoring your progress along taking the drug.

The nuance I'll say there is that the way that the companion diagnostic is defined in the US is different than how it's defined in Europe. So, when it's tied to a drug but used for monitoring one of the other, and I'm, for some reason I'm blinking right now, in one, geography is still considered a companion diagnostic and the other it is not. So, there's always these nuances.

We're getting back to class three versus class two. So, I think because that's tied to the drug, they keep that at a class three. The other things that fall into class three are those that of course relate to screening blood for donation and infusion.

If you think about it, it's like a companion diagnostic in the sense that it's trying to decide something that's going to go into your body. So, they keep that as a class three.

Other things, it might take you into a class three. The reason I went to that other explanation earlier is because either they're going to be doing this test and trying to determine a diagnosis based on no information, because it's a screening test or with other information as an aid to diagnosis.

And if you start reading the intended uses on clearances and PMAs, you're going to find that majority of diagnostic tests say aid to diagnosis because again, the doctor has a clinical picture of you, and this lab test is one of those pieces.

And so, it brings the risk class down because it's not the only piece of information being used to decide whether or not you have this disease or condition. So, but in a screening situation, I take newborn screening, it may or may not be considered higher class because there's really no other thing being used to, to do this diagnosis. So, some of those are still class twos. If they can have some special controls around them or, you know, how they look at them, maybe they require really large clinical studies.

And they typically do in those situations because in order for a screening test to happen. It's usually trying to find something rare anyway. So, you usually have these really large clinical studies.

So, some of them are class two s, but that's the one thing that could bump you up to a class three would be something where you don't have other information to help you make that diagnosis.

So. But for the most part, they're all class two.

Etienne Nichols: And I’ve heard you talk some about pediatrics too, about if you have any chance of misdiagnosing something, it could be potentially bad, not because the child will be in danger, but because it may be treated differently consistently throughout their childhood.

Could you speak to that a little bit as well, or.

Christie Hughes: Sure. So that gets into when we get back to harms and risk, thinking about risk management for in vitro diagnostics versus medical devices, but again, were in vitro and were indirect.

I used that word earlier, but I didn’t really go into it. So, when you think about risk management and harm to patient, you know, medical device is actually interacting with the patient, that seems easier to decide.

Harm. Oh, I burned them with my cauterization or whatever. Right. Vitro, it's not touching the patient. So how do I think about that? Well, really the only way to think about it is how accurate you are with telling the results. So, the main hazards are going to be false positive.

So, I told you were positive, but you really weren't, or false negative. I told you were negative, but you really don't have, I'm sorry, but you actually do have the disease, or I was really delayed in getting your results.

So that doesn't always come into play unless it's an urgent type of test. Right. But that's the other three. Those are the three main hazards that in vitro diagnostic manufacturers considered when they're doing risk management.

And so, trying to relay that down to harm. Well, if it's, I'm supposed to decide, maybe if I told you your glucose was okay, gave you a quantitative value that was in the normal range, but that was false and you were really low on glucose and you needed to know that there might be harm and that you needed some kind of treatment and didn't get it.

But it's, so it's a longer pathway that the hazardous situations that have to pile up on top of each other to get to that harm, it's a longer sequence of things than it typically is for other medical devices.

So that's another very big difference in in vitro diagnostics.

And so that's that. Oh, you were saying the other thing. So what? One of the examples I was giving you when we spoke earlier was going back to newborn screening if someone were to.

And this is why this gets really important when you're designing your test. A lot of tests are positive, negative. And what that's based on is there's usually always an underlying quantitative number.

Like in molecular tests, there's cycle thresholds, and it goes through all these different cycles of amplification. And then it looks for things as it goes. And at some point, you're making some kind of determination of, okay, at this point, it's either considered, if it's above this line, it's considered a positive, or it's below this line, it's considered negative. And part of the struggle in developing a diagnostic test is deciding where the best place to draw that line is because it's never going to be perfect.

Everyone has different situations. You may not get enough sample, and that might lead to not having enough to test. There’re all kinds of things that can go into affecting your, your test, into interfering substances.

All kinds of things can happen. So, you know, the manufacturer is always having to find the best cutoff for that above which you're positive, below which you're negative. And sometimes when you're in a screening test situation versus a diagnosis, you have some different leeways.

Because in a screening situation, if you're not getting the H and P with the patient and don't know any other information you have, you, you kind of want to make sure you never don't catch somebody.

So, you have to kind of take the risk in getting more false positives just so that you don't miss a patient because they're not coming back to you. Right. Whereas in an aid to diagnosis, there's other things helping the doctor make the decision.

You might take the risk to go put your cutoff in a different location, for example. So, what I was telling you about as an example for newborn screening is if you go for a false positive, you know, you brand new, beautiful baby new parents, you're already scared, and you don't even know this is happening.

You forget, you don't even know. You don't know that happened or in the room, and they drew the blood on the heel, and you were mortified because you're screaming their head off.

Etienne Nichols: I remember that.

Christie Hughes: But, you know, they screen every state test for a whole battery of tests at state by state. They decide what they want to test for and pay for. Because if they just, if it's positive, the state pays for the treatment for that baby, at least 18 years, if not life.

And so, if you were to tell a new parent that their baby was positive for one of these congenital disorders, and they go get the full workup and they're not, there's always that scare for you that they found something at one point in time. So, like, every time they sniff or cough, you're like running to the doctor because, oh, you know, because maybe they really did have this or something else.

So, what they've seen over time is that psychologically what it does to parents is it really freaks them out. And they always treat that baby a little bit or that child differently if they run into the hospital a little quicker than maybe their sibling, all because of that false positive test.

Right. And so, there's always, when you're thinking about risk management, to me, that needs to go into that thought process as well, because the psyche, you know, if you were told that you have HIV and you found out you really didn't, you're forever probably traumatized experience, but the opposite is true. If you're, if you had cancer and they didn't find it, and then you get further down the road with it and you're in a situation where the treatment is much more harmful to you or too late, that's also bad.

So, you know, these are the kinds of things that individual diagnostic manufacturers have to deal with. And going back to the LDT situation, what I don't appreciate or fully understand, you know, labs are held to a different. To different standards. Literally, they have ISO 15189 and they actually have different risk standards for people running lab tests, which is different than ISO 1345 and 14,971.

As of today, if those labs are choosing to use 1345 for design controls and 14. Nice venue. And for risk management, that's by choice, but it's not by requirement.

And so, are they really going through all those same processes as an IVD manufacturer is expected to do? And I think not trying to be any kind of advocate for one way or the other.

I'm just devil's advocate here.

You know, that's where some of FDA's concerns get validated. Right. They're not held to those types of standards.

So, you know, these labs don't have any proven to the FDA. But I actually am doing that. Right. Because they're not. They're not looking at them and it's CMS that's looking at them and they don't audit to those things.

Etienne Nichols: Yeah, that makes sense. So, when you really, what I've been hearing a lot is risk management is obviously a big part of medical device manufacturing. And I don't know what the translation is from a medical device to IVD.

You talked about three the biggest hazards or harms, and it is kind of weird for me to think about, okay, this is all happening outside the body. So, what all do I need to think about when I think about ISO 4971 and its definition of harms, it’s not just harm to the, to the person themselves, it's harms to people, property and the environment.

So, I mean, this is an interesting thing because with QMSR, the quality management system regulation that the FDA is now they're, they're taking part 820, which governs the. Or is the regulation for medical devices.

They're taking that and harmonizing with 1345. So, by extension they are harmonizing with 14971 as well with their definition of risks and their requirements around risk management, because that is the risk management for 1345.

This is a long-winded answer and I'm going to end my TED talk here in just a second. But our long-winded question, that being said, is that, is that one of the biggest things to think about as far as differences, you being a little bit more creative in your approach to risk management, can you speak a little bit more to that and maybe tell us what else, what else do we need to be thinking about when we talk about the differences between these two worlds of medical device and then the sub world of IVD?

Christie Hughes: Sure. So, if I backed up for 2 seconds and thought about just QMS in general, you know, the standard structure of a QMS is the same between med device and IVDs, and that's the same before MDR and IVDR.

So, you know that you've, you've got all the same elements. Those are pretty much addressed the same. The differences come down to all of your design and development, which includes risk management.

And then, you know, the questions you would ask yourself for, for looking for safety reporting, those are different because you have to answer the questions differently. And something that's potentially reportable is thought about differently again, because it's this longer indirect pathway.

Right.

So, with respect to what you were asking. So, there are, even if you look at, you know, ISO 14917 has the tr, the 24 917, I think. And so, for IVDs, it actually has its own annex because again, they're looked at so differently.

So, you now, IVDs can still apply some of those other things. So, if you have an entire instrument system, what's, what's been always fun for me for IVDs is I was with a company that had their own technology.

So, we, we had hardware, we had an instrument, we had software running it, and we did all the chemistries and biologies to make the assays as well. So, I got to see all the sides of it and be part of all of that and learn from all these very smart people.

So, it's exciting because you got to see all those aspects of a product and not just, you know, just looking at, oh, yeah, another spinal implant, right. And I get to see all the whole broad spectrum of it.

I keep losing myself. But when it comes down to risk management, so you do apply some of those, like, for your instrument, you're still looking for electrical hazards and mechanical hazards, so you still have to add those in, which are some of those other annexes.

But then, and then there's software. So, the same for software. But the thing you have to now add is also what happens when I give that false result, whether positive or negative, because the harms are different, right. A false negative may have a bear, a different harm than a false positive for each test. So, you can't just broadly say, oh, if it's a false positive, it's forever going to be this control mitigation.

That's not going to be the case. It does have to be test specific, because it just depends on what it is.

Etienne Nichols: That makes sense.

The other thing I was thinking about is design controls, because risk management, I mean, in a good world, and I say ideal world, but it shouldn't even be just ideal, but risk management should be feeding your design controls. Not always the case. I've seen that in reality, risk management, we're getting there.

It's getting better, right? Sometimes their own. Their own activities and they don't always meet, but they should be feeding each other. But when I think about design controls again, I think about a scalpel that I hold my hand.

I could probably bust out user needs and. And design inputs and start starting on the drawings with the design outputs just to. Just with my mechanical engineering background. But now maybe I'm not creative enough.

How do I start applying those design controls to an IVD?

Christie Hughes: And that's something I saw at my startup company I was with for so long, is that, you know, we had these brilliant engineers, and I had actually worked in a laboratory before.

Dude, you don't know what you're talking about. That's great, but I'm gonna.

Etienne Nichols: That's not what you said, is it?

Christie Hughes: I might have been a little bit more cursed at that time.

They all love me now. It's okay, but you know, for example, the software guys in their little world programming away, and you look at it, and I remember when we got to the touchscreens side of things and I looked at, we're all like, you know, the person in labs can have a glove on, which is going to make their finger a little fatter. They're not going to be able to click between those two little buttons you have so close to each other.

Right. So, it, you know, this is where it comes down to it's really important to interview your users and not just make assumptions based on. I'm a smart engineer and I know what I'm talking about, because even with the scalpel, have you ever been a surgeon?

Have you ever been in an or…

No. You should always, because I did marketing for a little bit, by the way, you should always have a focus group, interviews. You should go out and meet. I remember we had one project where we all, we flew out and met with all these different folks from different labs.

I got to see so many amazing labs and it's like, I'm going to go back to the lab.

I hate night shift, but, you know, to get in the face with the user and hear their concerns and see them work in their daily, day to day things and understand their problems and is so important to designing any product, if you're not doing that, you're going to end up with higher. Yeah, higher risk, higher levels of adverse point, or at least complaints if you're not understanding their problem that you're trying to solve.

So, it is very interesting and different, but there's also the span of. There’re different types of users for lab products. So, we have a professional user. There’re also classifications of devices by CMS, which is who does a reimbursement for lab tests and who regulates those medical laboratories in the US.

And they have high complexity, moderate complexity, and then CLIA waived. CLIA is just the regulation name for laboratories that came out in 1988, CLIA 88. The high complexity, that's gonna be anything that doesn't fall in the lower category.

The default to any test is a high complexity. In fact, when you put your product in for 510 clearance, part of the assessment that's done before you get your clearance is an assessment to decide if your test is a high complexity, moderate complexity, and if you want Cleo waiver, there's actually a separate application process for that. And what that gets down to is, you know, each lab employs different types of lab people. There’re different levels of lab people, those that got a bachelor degree and got their board certification.

Those that got an associate's degree in their board certification, I really, that's only two levels a lot in the US. And so, some of that kind of leans into maybe what they're allowed to do or not to do within that lab.

And so, they do have to pay attention to that. And CLIA labs as to what they're testing, what they're claiming to be testing, and then how they train the people and who's qualified to do the different tests.

Having said that, as part of user requirements, if you have a test, and everyone saw this with COVID if you, and then there's over the counter, which I didn't even touch on, but you got to understand your user.

Is your user going to be high complexity user? I can be. I can take some risk with not being dumbing down my device use so much and making my workflow too easy.

I can give them a complex workflow, or do I need to make it to where it's a lot more dumb proof? And I hate using that word, but I can't think of a better word at the moment.

Etienne Nichols: But we'll go with.

Christie Hughes: So, that was in the back of my mind because I just didn't know. We're talking about Greenlight Guru, who knows what Coca yoke is. So, for a CLIO wave test, for example, those are actually allowed to be tested by non-lab people.

So that has to be brought way down because that might be tested in a physician's office lab by an LVN or a clinical assistant. So, you can have anything from the doctor testing it down to a clinical assistant with maybe a six-week certificate.

So, for those, manufacturers have to be very specific in how they design those to make sure that they're very simple to use. And there's very different requirements on those tests.

There's different guidances for those. There's additional, a whole long list of additional verification, validation and usability things you have to do for those tests. And you know, your labeling has to be 7th grade level things of that sort.

So, it has to be foolproof because again, you don't want a false positive or false negative on that COVID test or that, that HIV test that they came into the clinic for.

So, when it comes to those, you still need to understand the user and who they're going to be and then the environment they're going to be in if they're, if, if they're going to be using it in a clinic down the street, maybe they don't have this fancy fridge to keep the reagents cold.

So, do you need to make sure that your reagents can be stored at room temp?

Is it going to be a mobile device on a, on an ambulance? We better be able to take vibration. You don't, you're not going to be guaranteed they're storing your reagents.

Right. Either. So, they'll be able to handle a big range of storage temperature. Right. So again, user requirements are in risk management. In that situation, you really do need to think about how is it going to be used?

Who's going to possibly try. And, you know, you have, the off-label uses can go pretty astray too. Right. So, there's a lot of things to consider there. And then that brings you back to labeling, is very specific about what your intended use is and what your limitations are, how it can be used and not be used.

But it all comes back to risk management at the end.

Etienne Nichols: Yeah, yeah, no, it makes sense. It's.

Christie Hughes: You have to ask yourself the right questions to start.

Etienne Nichols: Yeah. So, what are the user needs are really interesting when you're talking about that. And then just when we talk about medical devices and we think about those requirements for those, you want to think about the whole user chain is what I call it.

That's probably not the right appropriate word. But thinking of supply chain, when you have supply chain, you have all the different little nuts and bolts. Everything has to come in a certain way.

And you think about all of the quantities of each part so that you can determine how many parts can I make this month? You could tell I probably worked in manufacturing, or maybe you can't because I can't verbalize it.

But the same thing with your, your user chain, uh, with medical devices. I want to know who is going to have my hands on this scalpel after the surgery? Who's going to resterilize it, who's going to ship it to you?

All of these different things, it sounds like. I mean, the same thing with, with when you're, when you're building out an IVD, maybe even more so with the high complexity.

Low complexity. Complexity is really interesting.

Christie Hughes: Yeah. Really. The thing that comes into the. On that, that part, the trickiest part is that we just have these reagents that are labile. And so, the supply chain there is what becomes critical.

Can I, can I, you know, when we, I remember being in my small company, we're like, we're going to branch out to Europe and starting shipping things over there. Oh, things don't get there overnight.

Oh, it takes two days. Ooh, we didn't think about that in our shipping validation. Oh, man. You know, so, yeah, the labile reagents. Yeah, things take a turn, and then again, I'll never forget, I was so horrified. You know, we had self-service engineers because we had instruments in the field, and I don't know if I was doing a ride along or I think, I think some of us were auditing together because it was a supplier that was of interest to them as well, and talking about how they would throw the controls and calibrators on their dashboard.

So mortified because they were supposed to be stored in the fridge and.

Yeah, you know. Yeah, that was an interesting insight. Like, oh, you know what? We need to start including the field service engineers as part of our input to our user requirements.

They have needs and then to that same effect, you know, when they were out in the field trying to, we had a laser-based instrument, and those were a little sensitive, and so they were out there realigning those a lot in the very beginning.

And, you know, when the engineers were like, we can put manufacture it and get as small as possible, well, the problem then became when you had to deconstruct it to do service on it, they had a hard time getting to the parts, so they hadn't thought about the needs for the service engineer to get in there and do things.

Plus, there's the laser. Once you take the case off, the housing off, what does that do to your eyes and your laser safety? So, you know, being, it was interesting being part of this startup company and all those growing pains, learning them all the hard way teaches you a lot.

So, yeah, there's a lot of things to consider for your users and your ability to manufacture quickly or efficiently, and then service it, if it's in the field, what's going to be serviceable?

How often do I need to service that? What has to happen for me to service it? And then in making sure you include all that in your consideration, not only for your design requirements, but definitely for your risk management and control mitigations, that's really interesting.

Etienne Nichols: I love the, I love the real-world examples of throwing the control on the dash. Yeah, I can see that being.

Christie Hughes: I can just picture my own face when they said that.

Etienne Nichols: If we zoom back out and look at the topic, this is the overall topic. Learning to speak IVD. Obviously, this isn't something you could teach somebody in 30 minutes. Your 25 years plus of experience is hard to transmit in a few minutes.

What do you recommend people, or where do you recommend people going to learn more about how to speak IVD? Are there resources you use a lot? We can put them in the show notes, but.

Christie Hughes: Oi, that's a really good question.

You know, I think my 1st, 1st thing that comes to my mind is if you're already a regulatory person, take advantage of the fact that the FDA publishes decision summaries.

Go out there and look for, you know, recent IVDs that have been cleared and start reading those decision summaries and just see how different those look. And you'll also see in there the expectations for the studies they have to do.

And you're going to be, your mind's going to be blown, I promise you, because I know that my mind's blown, that all IVDs have to do a clinical and not all med devices do, and we're in vitro.

That's always blown my mind.

So, I think that's where I'd probably start. I don't know that there's. I'm wondering if CD, CDRH learn has anything on IVDs. I don't know if they do. It's a good question that or you may just have to come to Etienne and mine's next us essentials for reps and do the breakout for sure.

Yeah, I have to be honest, the problem with being in the IVD world is that you have to be extremely resourceful because there's not a lot out there, you know, there's a lot for med device.

And even I take Europe as that example again. They put out some guidance for those guys, but we're still waiting on the IVD side. EUDAMED has capabilities for med device that they don't have for IVD yet.

So, we're just always kind of the, I hate to say the stepchild, but that's kind of how it feels a lot of times. So, then that, all I can say is reach out to me.

If you have a specific question, I can try to help you there. But yeah, I think the fastest place to get some up to speed would be, you know, just looking at and even going back and looking at the COVID examples, all of their labeling is public on their, on the EUA website.

But to be honest with you, a lot of people didn't even know what an IVD was until COVID hit. So that's helped a lot of people come up to speed on even knowing, oh, what is this?

Oh, let me learn more about that. It's really important. I never realized how important this was, you know, so, pay attention to those lab results. That you get.

Etienne Nichols: That's really good. So, I just looked up the CDRH learn. It looks like they do have an in vitro diagnostic section that actually was updated today. And I assume it's with the, the virtual town hall on IVD development and IDTs, but.

So that is, that's a great resource. I don't always utilize CDRH learn, so that's, that's a good point. Those who aren't aware you can actually subscribe to get FDA updates.

So. And they have a lot of different checkboxes. You can, don't subscribe to everything because you will literally be inundated with emails from FDA. But that's another way you can keep up to date with their decisions. But the EOA and the decision summaries, that's really good.

We'll put those in the show notes so you can have links to those, get to those easily, and if you're okay with it, we'll put your LinkedIn, and people can find you and reach out to you directly with questions. So that's great. Any last piece of advice to someone who's new, maybe me, if I, I'm like, hey, I want to work for an IVD company and I worked on neurosurgical equipment.

Now I want to move to this. But what's, what, what do I need to do?

Christie Hughes: Say as a consultant, there's going to be a lot of work for us. So, job security, because the IVD manufacturers have still not been coming to the notified bodies in Europe to get up to speed and transition.

So that's going to be a bowl of support. And if FDA pushes forward with where they are, these labs are going to need a lot of help. And I was listening to Shannon's, you know, your podcast with Shannon and just, I wish there was a, you know, a way to bridge between, you know, us and them. Me having the industry experience, having been in the lab and being in the lab and being probably his hand force and having to do this, we're going to have to find a way to work together to make, make it a little more smooth for everyone.

Because I understand that, yeah, the terminology is different, the expectations are vastly different. And it's all nuanced things. And it's not that people can't get there, but if you're not willing to open your mind to the shift, you're going to have a harder time.

So, it's going to be people having to kind of let some guards down and take that in and be willing to make some, some changes. But I don't think they have, they don't have to be as maybe significant as they think they are, but it is going to be a shift in their mindset and in their culture, and those are some of the hardest changes to make.

Etienne Nichols: So that's, that's a very good point.

It'll be interesting to see how it all changes and how it plays out. So, we'll keep you updated. Maybe we can do a follow up episode after some things shake out and settle down.

Well, thank you so much, Christie. Really appreciate you coming on the episode. And those of you been listening, you've been listening to the global medical device podcast. We hope you have a great rest of your day during check out the show notes.

We'll try to put lots of resources in there for you and we will see you all next time. Take care.

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