#332: Regulatory Strategy and the Advantage of Diversity in MedTech

Nada Hanafi: Yes, with the use of pulse oximeters and they don't work as effectively in different skin tones and that's really unfortunate. And led to worse outcomes. Such a simple device. But the validation for that is typically in healthy humans. And who volunteers for that? It's Caucasian young men. Well, that's not the intended patient population, right? When do you go to the hospital to get and the first thing they put on you is a pulse oximeter. So a simple device. But that led to really dire outcomes that could have been prevented had we thought about the unique aspects and considerations of the different patient populations.

Etienne Nichols: Welcome to the Global Medical Device podcast.

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Etienne Nichols: Industry is nothing if not unique, so we built software that works the same way. Greenlight Guru is the only quality management system designed by medical device professionals to meet the unique needs of medical device companies. Our cloud based platform allows companies to bring safer products to market up to three times faster, while reducing risk and lowering cost. Visit www greenlight guru today to request your free personalized demo of Greenlight Guru. Hey everyone, welcome back. This episode was recorded live in San Jose, California during our true Quality Roadshow. If you're not familiar with what that is, we still have two stops on our worldwide tour amsterdam and Orange County. I'll put links in the show notes so you can find it. This was a fun conversation. This is an interview with Nada Hanifi, the Senior Vice President of Verinex. She is also the mentor and sponsor of Medtech Innovator.

Etienne Nichols: Maybe not the mentor, but she is.

Etienne Nichols: A mentor and sponsor of Medtech Innovator, a co founder and board member of Medtech Color, which is a nonprofit organization that aims to advance the representation of persons of color in the medical device industry. She spent twelve years at the FDA, where she was a CDRH liaison and subject matter expert to FDA's Office of Women's Health and the Office of Minority Health. Nada also holds a Master of Science in Biomaterials, a Bachelor's of Engineering in Biomedical Material Sciences and Engineering from Queen Mary College, University of London, and her Master's of Public Health from Johns Hopkins Bloomberg School of Public Health. She's passionate about the industry and an incredibly well qualified regulatory strategist. So I hope you enjoyed this wide ranging conversation with NEDA Hanefe.

Etienne Nichols: Welcome back to the Global Medical Device podcast. My name is Etienne Nichols. I'm the host of today's show. With me today is NEDA Hanifi. I'm excited to speak with you today. I guess before we get into the overall discussion today, why don't you tell the audience a little bit about yourself and where you come from.

Nada Hanafi: Thank you so much for having me. Good afternoon everyone. So I'm NEDA Hanifi and I am currently a senior vice president for Veronax, and we're a full service provider for the Medtech industry. And my focus is really within the regulatory quality, clinical. And prior to that, I used to be at FDA, where I say I grew up there. I spent over twelve and a half years at the agency predominantly CDRH Center for Devices and Radiological Health. And I started in a traditional route as a lead reviewer and then transitioned to the office of the center director, where I led different programs and policies with a unique kind of interest in the health of women, special populations, and pediatrics. And by training I'm a biomedical engineer, as many folks probably are here. And I also have a master's in biomaterials and in public health that I got while I was at the agency.

Etienne Nichols: That's fantastic. And I don't know if you get celebrity status very often when you go to conferences, but we always love to speak with people who are at the FDA because sometimes we look at that as something of a black box. I don't know if that's completely predominant throughout the industry, but I know a lot of people see it that way. So I'm curious if we could speak a little bit to your time at FDA. You said you grew up there. What are some of your favorite memories? Do you have any things that stick out that you really look at as formative into your career that occurred there?

Nada Hanafi: Sure. So we're not a black box. I still keep saying we, but they're not. They're just human beings. They're just like you. But they are tasked with a mission to protect and promote public health, and it's a pretty serious mission. They are kind of the gatekeepers to ensure that products get to market. When they get to market, they're safe and effective, and then when they're on the market, they remain safe and effective for their intended use. So I learned a lot while I was at the FDA. I think anyone who works in federal government, you're in a position of service, and we take that duty seriously. But I also had a lot of fun while at the agency, and you asked me about a happy memory. There's a lot of them. There is one that I'd like to share. While I was there, and when I transitioned to the office of the Centre Director, leading up different strategic priorities, I had the pleasure of working with the DoD Department of Defense, and they have this group that's called I'm probably going to butcher it, but it's the Defense Materials Program Office. And what they do is they collect any kind of failed devices or medical products from the combat field. They're sent back to them to do investigations to see if the reason for their failure or if they caused any kind of adverse events. And I'll just speak to one specific one. It was about Tourniquets, and imagine it's military personnel in combat situations. This is a life saving device, and they were seeing some major adverse events. So we managed to set up a communication with them, share the information that they were seeing, their analysis of the issues, as well as connect them with our post market group that looks at MDRs or the more database and see if we were seeing similar issues, and then also with our compliance arm. And there was like a whole you think of it TPLC or total product lifecycle group assessing these issues. And we managed to get some resolution and move the issue forward so that we could ensure that these tourniquets were going to work as intended in a very high risk situation on the combat field. And that was great learnings. And one funny thing that stands out, we all had a workshop, and we went to one of the army base and met with this group that we'd been engaging with for a while. And when I met this senior know, major general, really nice, staunch man, and.

Etienne Nichols: He'S like, you're, NEDA.

Nada Hanafi: And I said, yes. And he said, I thought NEDA was a whole department at the agency, which was very interesting and funny, but I share that because people who work at the agency tend to be really dedicated to what they do. And it's a couple of people, you think there's a lot of resources, but no, it's like one or two person doing the best they can to live into that mission. So that was one memorable experience.

Etienne Nichols: I love that. And I love that you zoom in on the human side of things with the FDA, because like you said, they're human beings. Everybody who works there is a human being. And I really appreciate that story. It really humanizes. It so if we were to zoom out a little bit while you were there, I'm sure you understood all of the different regulatory ecosystem that you were living in. I'm curious now, having stepped away for a little bit, you still use the word we, but having stepped away for a little bit, do you see any changes in whether it's the relationship or how things are approached? Curious what your thoughts are as far as how things may have changed or for the better, for the worse, whichever way you want to go.

Nada Hanafi: Yeah, great question. And I say we. I speak to FDA on a regular basis, and I have some on speed dial. Unfortunately, they get annoyed with me, probably. But there has been an evolution. I think in the past, most folks were looking to go outside the US. And thought there was an easier path to get their product on the market. But I think things have shifted. FDA took a concerted effort to look at our programs, our policies, how we conducted and deliberated, and came up with our decisions and tried to bring more transparency and predictability to that. And with that came a lot of more guidance documents to explain how we do business, how we come about our decision making both for industry as well as themselves. So to kind of standardize the approach and you've really seen that shift where now I think industry is coming to the FDA where it's more predictable and they're more consistent in the questions that they're going to ask of you to get their product through FDA is probably a lot faster than going into the EU or other. So that shift I think has helped with the innovation aspect. They updated their mission statement to say we want to get products of the public health, most public health importance first in the world, in the US. And I think they've really lived into that mission with the changes that they've established.

Etienne Nichols: Yeah, that's really interesting. So being regulatory strategist now, I'm sure your focus, you probably had a global focus before, but it was hyper focused on the US. Do you look at things a little bit more globally now, being on the outside? I don't know why to use that word and if so, how has your perspective changed from a global perspective?

factor was the happenings of: 2020

Etienne Nichols: Yeah. So I want to ask just a little bit, one layer deeper I guess. So challenges and opportunities for medtech from a global standpoint. Obviously we typically think EMDR we talk about the challenges related to that. I was wondering if there's anything else that kind of stands out to you when you develop a regulatory strategy or if you'd be interested in even just kind of talking through how you develop a regulatory strategy and what some of the obstacles and challenges people may face.

Nada Hanafi: Absolutely. I wish I could ask this group, oh yeah, but I get some good insight. So yeah, regulatory strategies are what we call a roadmap to successfully commercialize your product and get it to the market in a least burdensome. So I use FDA terms, but least burdensome manner, what is the minimum amount of data or evidence that you need to generate to ensure that it is going to meet the requirements? So when we're thinking about regulatory strategy, the first things I tell any client is, what is your device description, your product description, understanding how it functions, the specifications, and then tying that back to your intended use and your indications for use. Two words that are sometimes used interchangeably, but they do mean two different things. Intended use is the basic functionality. What does my device do? I'm a scalpel. I cut indications for use. Is everything associated with how that scalpel works? The who, the how, the where, the when, frequency of use, is it RX prescription or is it OTC, the environment of use, who's using it? Those are all kind of claims that you're going to have to substantiate with that evidence generation. I know I use a simple example of scalpel. That's a class one exempt device. It's class one exempt when it's in the hands of a physician, right? So that's the critical piece. So it really stems from there understanding what your product is and how it works, and what disease state, what patient population, who's using it. I e. That intended use, indications for use, and then you can develop what's my pathway to market, what's the evidence generation plan, and so forth. So those two are really critical. If you don't have those, then you start to go in this cycle of never ending, not knowing, or pre sub cycles with FDA, and kind of it's a downward spiral.

Etienne Nichols: And so I guess once you start developing that regulatory strategy, you know what your device is, you know how it's intended to be used, who it's going to be used on. At some point, it becomes something of an economic question. And do you get into the economical side as far as determining how are we going to return a profit and where will we go to do that? Is that part of your so that's.

Nada Hanafi: Part of veronec, and it's a fantastic question. So yes, there's the regulatory strategy, but in parallel, you should be thinking about your commercialization strategy, right? Your market access strategy, your reimbursement strategy. You could get it cleared or approved or granted, but is anyone going to pay for it? Right? So that needs to be done in parallel. And the requirements from a reimbursement perspective are going to slightly differ to what FDA's requirements are. They're going to be looking at really more outcomes related aspects. So if it's a device that's going to require some kind of clinical data, it makes 100% sense to be thinking of what's the study for FDA to get you to market. But then what are the requirements from a reimbursement perspective? What's the specialty or that industry going to want to see? I'll say urologists. They love to look at literature. Did you publish on this? Did you study it before they'll start to use the products? So you got to understand which market you're going into the speciality and how are you going to be able to convince them to actually use your device. And an uptake and lift so they go parallel in parallel. But then I also jump back because I'm FDA or regulatory centric. If you don't get through FDA, you're not going to get paid. But they go hand in hand for sure.

Etienne Nichols: Absolutely. There's a certain baseline you have to meet. Yeah, that makes sense. Okay, so that's what you do at Verinex. I know you also have something else that you co founded, Medtech Color. And it may seem like a non sequitur that I would bring this up, but I am curious. Well, first of all, I want to hear a little bit about that, but I also want to hear how it ties into regulatory strategy as well, because I know there's a tie there. But can you tell us a little bit about Medtech Color and the mission and what motivated you to co found this?

rofit, and we were founded in: 2018

Etienne Nichols: So from a regulatory strategy perspective, what would be the advantage of trying to make sure that you are inclusive of all these different possibilities? What is the regulatory strategy advantage?

Nada Hanafi: So I'm going to take it many people might jump to clinical trials. I'm sure you've heard about the lack of diversity in clinical trials, and there's a lot of emphasis on that from regulatory agencies, from funding agencies, from the big industry players. But we like to think of it upstream. Clinical trials are downstream, and it's too late. You've missed your opportunity. So upstream, when you're designing your products, right, in that ideation phase, when you're thinking about, again, what's the device, what's the patient population? Does it disproportionately impact a specific group? Does it disproportionately impact women and kind of segregating or determining your true patient population? You've got to think of their unique needs there, right? And thinking of it at the design phase will definitely lead to downstream benefits, because then if you do need to do a clinical study, you know who you're actually targeting and intending to use this product in, and it's too late at that point. And how does that impact reg strategy? Well, FDA now has a strategic priority that's related to health equity. It's going to become law. It's going to become in a statute where you have to explain to FDA what's your plan to include different racial and ethnic groups in your clinical studies. So this is a requirement, finally. It's taken us this long, right? But products need to work in the population they're intended to be used in. And one key example that unfortunately, the pandemic highlighted, where we saw disproportionate deaths and mortality morbidity in the black community was with the use of thank you so much. Yes. With the use of pulse oximeters. And they don't work as effectively in different skin tones, and that's really unfortunate and led to worse outcomes. Such a simple device. But the validation for that is typically in healthy humans. And who volunteers for that? It's Caucasian young men. Well, that's not the intended patient population. Right? When do you go to the hospital to get and the first thing they put on you is a pulse oximeter. So simple device. But that led to really dire outcomes that could have been prevented had we thought about the unique aspects and considerations of the different patient populations.

Etienne Nichols: So you already mentioned doing it early with design, and my mind is kind of going back to what you said earlier about intended use and indications for use and how this could be potentially a subset of your indication for use, I assume. What is the actual practical, or what does this look like in reality, like when you actually go through sit down. Okay, I'm going to try to cover all the bases here. What does it look like in the design and development process? Can you give us a little nitty gritty in the weeds?

Nada Hanafi: What a great question. I think it's going to depend. Right. It depends again on what the product is and how it's intended to be used and is it an implant or is it a wearable, is it permanent or is it a temporary device? And I think it's all these considerations. And I'm sure a lot of quality folks in here there's checklists, but the basis or the core of it is really your risk assessment, right. When you're looking at your user needs and what risks might be associated, what's the likelihood of those risks, and then how are you going to mitigate for those risks? Right. So I think it starts there. And hence, if you embed this thinking of are there different considerations based on the patient population? I mean, sex being an immediate one, right? Women are not little men. Let's get over that. And women are also not just their ******* and their uterus and ******. It's not bikini medicine. Women will be exposed to devices such as hip implants and knee implants and any other cardiovascular devices. So you've got to consider their unique needs. And a lot of times I think design groups might think of anatomy as the first differentiator, but we want you to go deeper because there are racial and genetic differentiators that you need to take into account. So I think it's groups coming together and challenging the mindset. Right. Even if you look at in the Ophthalmic space, a female eyelid is very different.

Etienne Nichols: Really?

Nada Hanafi: Yes, and I'm not an ophthalmologist, but when you speak to different people, there are very unique considerations. And then if you layer on by race or by ethnicity, there's even more differences. Right. And then add another layer of the social determinants of health right. And the environmental aspects. So there's a lot of considerations. And I think companies and innovators miss on opportunities and will fail in the long term if they don't consider these items up front. And of course, then you might say this is just overwhelming. But that's why I said it really starts with what disease state or what problem, what pain point are you trying to address and defining that problem. So I'll just add one little thing. I think a very well defined problem is a half solved problem, and that's where the effort and focus should start.

Etienne Nichols: I love that. Early in my career, I had a mentor who told me the heart of the problem is the seed of the solution. And so really focus on the problem and forget the solution. Just focus on the problem. So I love that. So if we zoom out a little bit thinking in regulatory strategy, I mean, obviously we can go deeper with this. But again, I'm curious, as a regulatory strategist, whether it's in this area or other areas, what are common problems or obstacles? You see companies getting into that. You just know. I saw this at the FDA I see it now. I know this is a problem people are facing and getting into.

Nada Hanafi: So one thing I see is people trying to move fast. Speed matters, time is money, especially when you're a small company, say, and we want to get to market now, now, and maybe they haven't really defined a problem. So a lot of what I tend to do right now, which is unfortunate, actually, is what we've termed regulatory rescue. They've had several interactions with the agency, and they haven't moved them forward, they haven't moved the needle. And when we dissect it, they couldn't explain their product, how it works, what it's intended to do, and they couldn't bring FDA along with them because they probably didn't even know what their product was or it's intended to do. And they're like flip flopping around and it's like, take the time up front, go slow to be able to go fast. And I think I will sound like a broken record. Many who know me will say this. It's always that product description, intended use, indications for use, knowing that your intended use or your indications may evolve, especially if you have to conduct a clinical study, because it depends on the outcome of that clinical study. It's like the last item that you're negotiating with FDA. If you're just about to get clearance, they might say, oh, we've changed this word, or we need you to remove this sentence. But it's all about the evidence generation, so it's the last thing. So it's always your proposed indications, intended use, and it evolves based on the evidence that you have to support it. But that's where I think you haven't fully decided what you as a company are tackling, what pain point, and then you can't fully explain that to FDA and you get into this unfortunate cycle. And it's frustrating on both sides, but it could be prevented if you take the thought up front to kind of really define your lane and stick to it.

Etienne Nichols: Do you have any specific examples that you've seen where people do this incorrectly? And if not, it's okay.

Nada Hanafi: This is a simple example. So you think of class one exempt devices, your class one exempt. That means you don't have to submit a pre market notification or 510K, unless you exceed the exemptions, right. And you have to figure out how you exceed those exemptions. This is a tricky one, because if you're class one exempt, you're likely there's no predicate out there, right, because the majority are class one exempt. You might find an OD one where you were exceeding or you were going for a claim that really did require substantiating and that FDA would need to review. And I think it's in those tricky spaces where I've seen some clients submit a misthought out 510K. Go ahead.

Etienne Nichols: Well, just curious. So exceeding meaning I actually plan to do more with this device than maybe.

Nada Hanafi: I'm saying exactly than what the CFR code of federal regulations, identification of that product, and you have to do that assessment. And again, it goes back to benefit risk profile and your risk assessments to determine if you're exceeding it. And then you have to submit a those can be very tricky. I think FDA is less familiar with them. And then I see in industry, a lot of times they're less familiar with what the approach is. So in terms of that, I'd say think about what is the ROI, what is the return on investment? If you really want to pursue these claims, is it giving you some market advantage? Right, that's worth it because it's not cheap if you're working with the consultant or for the time spent, if you're doing it on your own, and then just even in interacting and paying for five, ten K and the whole process.

Etienne Nichols: So thinking about that word strategy, does it make sense then to narrow your scope to get through and then potentially widen it later on with an updated you do strategy? I just talk to people.

Nada Hanafi: No, absolutely. So I think what you're speaking to is kind of a stepwise approach. So even if you're wanting the world and all the claims that you could get, one other thing we advise clients is, let's do an aspirational claims matrix. Let's put down all the claims that if you could have and get what they would be. And then you kind of have to tie that back to what's the evidence required to get those claims. And then you might be like, really whittling those claims down when you see the amount of work that's going to take. So doing kind of a stepwise approach. What's a minimal viable product that you want to get to market that can get through the process in the least burdensome manner with the least amount of information and data, and then you kind of expand on your claims once you get your first clearance granting or your approval as a PMA.

Etienne Nichols: I don't know if you guys heard that phrase aspirational claims matrix, but that's when you got to write down, I like that. That's really cool. I'm curious. So what are the consequences of getting this wrong? You said it's expensive, some of this additional claims. Can you give us an example of all the different expenses that whether maybe direct or indirect? Do you have any examples there?

Nada Hanafi: So, I mean, it's time, right? So if we just run through a case example you've submitted, even if it's in the pre sub world, you get stuck in pre sub land, back and forth, back and forth. Yes. You don't have to pay a fee to FDA to submit a pre sub, but you've had to either pay a consultant or work with someone or misuse your employees times to be developing these presups. Right. So time is money, as we said. So there's all of that and a presub. Typically, it's a 75 day process. Before you might get a meeting with the agency. Sometimes it's sooner, but then there's the upfront time that you created. So imagine that could be a four months process, right, that you've just killed. And in a year we only have twelve months. So you only got eight months left to execute on what you have to execute. I think it's that aspect of not having a strategy. Like I said, that roadmap to see where you want to go and understanding what's the evidence requirements to get you there.

Etienne Nichols: That makes sense. So I have a two sided question then. I want to kind of pull both your regulatory strategy but also what you're doing with Medtech Color. I'm curious, how do the best in class companies paint, whether it's a demographic or psychographic picture to really make this claim or just really from the design and development all the way through the lifecycle, how do the best in class companies incorporate that thinking?

Nada Hanafi: I think it's intentionality. It starts with having the open mind and having a talent pool that is diverse. Right. I think a lot of them also do a lot of needs assessment and community based outreach to understand, hey, if I'm going to innovate in this space, what's the biggest need? Right? I'm sure there's all about the ROI aspect, but then what is the biggest need and what does this patient group look like? I think a lot of times they'll also I know in the Pharma space specifically, they do use personas to kind of understand the different patient groups that they're going into. And I'm hoping more of the device world will start to do that. But I think it's also engaging with KOLs and going into the community and understanding how to engage with them, especially if you're going to be studying need to study, to conduct clinical studies. Right. Because you need those patients in your trials. It's building a trust aspect. The lack of trust in the clinical research enterprise, especially in certain racial groups, stems years and years. It's historical. So you have to overcome that and you have to step into it to really show that you're reputable. You're not just there to take these people's data and information and then get lost, but that you're going to come back and you're giving back to the community. So it's engagement in all aspects and wanting to do the right thing. But I think it's intentionality. The good leaders, the leading companies out there, they're intentional. They're saying, we're committed to diversity, equity, inclusion, and belonging in all aspects, and our products are really going to serve those most that need.

Etienne Nichols: Yeah, that's that's a really good point. So our goal at Greenlight Grew is to improve the quality of life. So that changes the way you look at things when you really think about your mission. So it makes sense. And also you mentioned something about the persona and I'd forgotten about this, but when I worked in drug delivery. I remember this. We had our PowerPoint with the person, their name, the way they look like, and so forth. And I remember those human factors tables from he 75 if I remember that right. Where the hand strength? We did a test once where they had me do the test strength as well. And I said, well, how'd I do? I was pretty pumped. They said, well it's not uncommon for your hand strength to decline as you get into your thirty s. And that was a terrible moment for me, but I love that you bring those things up. So the flip side of that though, so that's held some of the best in class companies. But you mentioned that this is going to become a requirement if it's not already. What are some of the common problems or the common mistakes? You also mentioned a specific example, the pulse oximeters. What are the common problems that a lot of companies you foresee probably continuing to do or so forth.

Nada Hanafi: I'm going to be hopeful and say that we're going to learn from our mistakes, so we're not going to be repeating the same mistakes. I think they'll learn the hard way if they don't follow the requirements. So for pulse oximeters now there's active discussion on updating the standards, the requirements, how we're actually going to verify and validate these products work, and the type of testing that's needed. And FDA is moving to if it's a pulse oximeter used in a pediatric patient population, they want data from that patient population. In the past we didn't want that. Well, we were missing out. Right. So I think you're going to have to, if you're not ahead of the curb, you need to get ahead of the curb or just get on the train and move along with it. Otherwise it's going to pass you and you're not going to be getting your products to market. So I'm hopeful that there is like a commitment, especially in Medtech. I think we're flexible, we're agile, we develop products at a lot faster rate than the pharma biologics world, and we can reiterate and have device changes and technologies evolve to really meet these new unique issues and improve health outcomes. So I'm hopeful and I think people aren't going to do it wrong. That's my wish for this world. Just do it right at the beginning. But if you don't do it right, you'll learn right. I think the most successful people are also those who've had failures, but they've learned from them and they're not doing the same mistake over and over again.

Etienne Nichols: Yeah, if you were listening to our previous panel, we talked about our favorite failures and they're definitely some smart people. They've learned from that. That's really cool. That's a good point. I'd like to ask the audience for questions, but I'll give them a second to think about it, because they've probably been hanging on your every word. So before we get to their questions, I'm curious. Do you have any last pieces of advice for those out there who are facing regulatory strategy, facing their design and development challenges that you mentioned? Any pieces of advice that you give these companies?

Nada Hanafi: Yes, actually, I think you mentioned trying the strength test. So I'm also a big believer in the lived experience and that patient perspective. So if you are designing something novel, consider having a patient join you in your design and engineering journey and being a part of it. I'll be a little bit women centric here. I think when you're designing for women's health or the health of women, you need to design with empathy in mind. You can say that's true for pediatric patient populations, for special populations, for digriatrics, any population. I'm not missing you out, gentlemen, but kind of designing with empathy in mind. And how are you going to get that real lived experience, having a patient join you on that journey? And they're going to be different needs at different stages in their disease journey. Right, but I think incorporating that patient perspective and voice early on will also lead to a better device and product at the end.

Etienne Nichols: Fantastic. Really appreciate that. We'll give the audience an opportunity to ask any questions. Do you have any questions? Yes.

Etienne Nichols: I think that the FDA has done such a good job of being more approachable and approving product quicker so that a lot of medical devices are starting to get approval in the US. Where ten years ago, they would have always gone overseas, maybe to the EU or perhaps Japan first. I was wondering. A lot of my customers have a really hard time when they have a device and they've shown efficacy in animal studies. Now they're ready to do clinical trials in humans. They all have to go overseas because it's really hard to get into human clinical trials here. Do you think the FDA will figure out a way to make it easier to start human clinical trials here in the United States?

Nada Hanafi: That's a great question, and I think FDA has been thinking a lot about this, and they have established programs to allow that. So you all may have heard of the early feasibility IDE program. So if you have to conduct a clinical study, and it's considered a significant risk study, you have to submit an IDE to FDA. And so they created this early feasibility program where if you're still in the early stages of developing your product, it's not fully flushed out. You can come in submit this ID. It's very limited. Maybe you're first in man where it's only ten or 15 patients. You show them some semblance of safety data in preclinical animal, and then you can study it in humans. And if you want to tweak the clinical study design or your device, you have to submit these changes to FDA to approve. But they turn around that approval in a lot faster timeline. Right. And that was an effort, a big policy push effort to try and encourage folks to actually do clinical studies here. I found that some people choose to go out of US. I have many clients who are in Australia. The government there incentivizes them and gives them tax breaks if they're conducting their clinical studies in their hometown. But I think I definitely and many of my fellow regulators like to encourage folks to think of conducting the studies here. I think the IDE review timeline is only 30 days. So it's a big comprehensive package, but FDA will either approve it or conditionally approve it or deny it. But you will get their feedback. They'll give you a list of questions, and that's their thinking of what they want to see. So it's only helping you move your product design and development forward in a more expeditious manner. So I think early feasibility is one great program that does encourage this first in man studies or first in human studies to be conducted here in the US. I hope that answers the question.

Etienne Nichols: Thank you. Nada, you talked about empathy. FDA has been issuing guidance for human factor and usability engineering, but they haven't really gotten into regulating that. Do you think they have a thought process where as they learn more, they might be regulating this field as well?

Nada Hanafi: Regulating the field of human factors testing.

Etienne Nichols: And usability and usability engineering?

Nada Hanafi: Yeah. And that's heavy. That's really interesting because right now the joke is that any device needs human factors testing or usability testing. And I see many of you quality engineers nodding your head, but even that would be a good test to have in product development, even if you don't need it for your regulatory submission. So, no, FDA is very much regulating that space and looking for human factors studies to substantiate that the products are safe and effective. And it's funny, I was actually looking at a de novo that was granted last year, and it didn't have any clinical testing requirements, which is strange for a de novo like in the special controls, but it had usability for everything, nearly. So I think the need for valid data as relates to can a product be used safely by that intended patient population or that group? The intended user is critical and very much on FDA's top list of requirements.

: What's the best practice for letter to file? So after you have your MVP submitted and got clear and you determine that other changes of sequences doesn't impact the performance of the product and then you decided not going to submit that as a letter to file instead you keep track of it is that really best practice or is there any other way that you can do the best practice? Before you submit a letter to file after you have your 510k?

Nada Hanafi: So a letter to file is an internal document, right? So you've hopefully done your risk assessments and gone through the 510K flowchart to determine that the changes you're making don't require the submission of a new document. That I know a lot of companies do a lot of letters to file appropriately, but good documentation, good document practice is critical because you can be audited at any time. And we've also seen where sponsors fail in that sense. And FDA thinks, oh, well, that should have really been a 510K. But where we hear a lot of letters to file, if the true risk assessment is conducted appropriately, I think there reaches a point where you don't want too many letters to file. And then people like to say, we do this 510K catch up, right? And those are not fun. They're not fun for FDA and they probably won't be fun for you. So considering that balance of when have you made too many changes, that now it's really not the same device that you got clearance for and catching it before you get to that stage and submitting the appropriate 510K, be it a special or traditional.

Etienne Nichols: Thanks for the great comments and advice. My question is about the FDA's regulation for more software based mobile software as medical devices or even AI based solutions, when there is need to train the model and the data could be different. And what if the data changes or the model variations, how is that being regulated into the future or now and into the future or what do you think is needed? Thank you.

Nada Hanafi: Yeah, thank you for the question. So the software as a medical device space or the digital health space is very fast and evolving, and I think everyone and their mother wants to be a software as a medical device based on our clientele. I think yes, training model is very important to our earlier conversation about representation. Right. Making sure your model isn't biased or skewed to one perspective and whatever you're studying isn't going to work in a specific demographic. So how you train it? First of all, you have to have separation on your training data and then on your validation data. They have to be two separate arms, and you clearly need to delineate that for FDA. But then also in terms of if you're making changes and involving that algorithm, do I need to keep submitting a 510K? It's a great question. I think it's the same assessment and thinking there FDA has what's really nice is, like I was saying, they're more predictable and more transparent. So they have issued a lot of guidances in this space and final guidances, which is nice, because if you're a draft guidance, you're really not in effect. And even FDA can't issue a deficiency or an additional information request based on a draft guidance. They should not do that. It has to be a final guidance. So they've made a big effort to put final guidance out, especially when it comes to the software space to kind of explain what changes may trigger a 510K or what is appropriate to be changing in your software, in your algorithms, without the need to go back to FDA. And it always ties back to that intended use. Right. Is the change impacting the safety and effectiveness of that intended use?

Etienne Nichols: I kind of have a follow up question. You kind of got me thinking a little bit here. So when you're training that model, you don't want it to be biased, but we also mentioned something earlier about being very more specific to something to your user population. So I'm curious about how you walk the line between specific to this user population, but also not being biased so that you won't and maybe it ties back to your indications for use. And I don't want to pile too many questions on here, but I want to add another detail, and that is with AI, it feels like it becomes necessary that we start differentiating. What is this versus that in that? Like you mentioned, I love your commentary about what is a woman. It's more than these body parts and then differentiating different ethnicities. How are we going to do that with AI and training these models? Or do you have any thoughts around that?

Nada Hanafi: Well, they're going to have to do it. I mean, a lot of AI is now used in the imaging space, right. You're looking at an MRI on X ray, and you're trying to feed up information or recognize an area that's high risk that a physician should focus on, like triaging software. Those if it's looking at any imaging, you need to make sure it's the representative images. Right? I mean, if it's in prostate cancer, yeah, you want to make sure it's men, but you want to make sure it's men of different racial and ethnic groups. So that's the training aspect. You need to make sure if there's a differentiation of how prostate cancer presents based on race and ethnicity, and it's something that impacts African American men at a much higher rate as well. So it goes back, like you said, into your intended use or indications for use and tying it there. But in modeling and in the AI space, I mean, FDA is very much on what was your data trained on and then what was it validated on, and is it representative? And maybe there in the imaging space, because a lot of it is on retrospective images, it's a little bit easier. Maybe they're ahead of the curve in being more representative in that modeling space.

Etienne Nichols: Yeah, just one of the interesting things to me about how to quantify certain differences is going to be interesting in the future rather than being subjective. I don't know. I'm just curious about that. My brain is kind of thinking about.

Nada Hanafi: It, but anyway, yeah, I know that machine learning is way ahead of my thinking, for sure.

Etienne Nichols: Any other questions from the audience? Okay, this has been really good. I really appreciate you coming on the show today and I'm excited to continue the conversation in the future. Thank you. You've been listening to the Global Medical Device podcast and we will see you all next time.

Nada Hanafi: Thank you so much.

Etienne Nichols: Thanks.

Etienne Nichols: Thank you so much for listening. If you enjoyed this episode, reach out.

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