Welcome to the Global Medical Device Podcast, where today's brightest minds in the medical device industry go to get their most useful and actionable insider knowledge, direct from some of the world's leading medical device experts and companies. Hey, everyone. Welcome back to the Global Medical Device Podcast. My name is Etching Nichols. I'm the host for today's episode. Today with me to talk about biocompatibility and an episode that we want to kind of call the biocompatibility brief, because we're not going to get super deep, although hopefully we'll get into some things that'll be applicable and useful. But with me today to talk about that is Marina Dyneko. The passionate explorer turned MedTech expert with a deep rooted love for chemistry and a mission to make medical devices safer through rigorous biological evaluation. Her journey began with curiosity and evolved into specialization and biocompatibility, where she sits at the intersection of science, regulation, and patient safety. So she has a strong background in chemistry and hands-on experience with a wide range of medical devices, and she supports teams in planning, executing biological evaluations in place. Right? Because we can't do anything properly and have acceptable results if we don't have this acceptance criteria set up in advance, you know? So I would say biological evaluation plan is very important and we have to have into it. Then going into details, because again, I face several times when I'm requesting usually a lot of information and regarding suppliers, regarding raw materials, technical data sheet, how many samples were sold during a specific period? Like a lot of different information. And for instance, I can find the gaps and it's important to go even deeper and find what are, for instance, disinfectants that are used to clean manufacturing lines. That's important. For instance, work instruction may not list these solutions, but we need to find what are used to be able to assess it, because there might be, as a case, when this disinfectant solution goes to medical devices and to the patient. So it depends. We have to assess all these things. And be attentive, yeah, for instance, again, just recently I have got results for cytodexicity and it was a component that contains silver ions. And I have got zero for cytodexicity. And by the way, silver ions are very known to cause cytotoxic effect. And then I was like, oh wait, what's going on here? You know, while we have zero, because I was expecting to have like three, but at least two, but you know, like three or even maybe four. And I have got zero. So I had some additional questions, like, hey guys, I was expecting to have been different results because of silver ions. What's going on here, you know? And we have to be very attentive to these details as well. So it's just several ones, but I would say they are most common, like to be attentive to the details, don't believe anyone, just check everything, go as deep as you could to find this information and don't be shy to ask questions and prepare your biological relation plan. Yeah. I love that specific or example, I guess, because that just kind of highlights the need for the critical thinking side of things. And I want to go into a little bit more details on some of these things and maybe how companies can miss the real signals. But I want to just kind of do a quick sidebar. And you can comment on this or not, if you like. But I think of obviously, biocompatibility, we think of physical devices. And as a mechanical engineer, that's where I prefer to live my life with physical devices. And so feel free to point, we can move on from this if you want. But software is a medical device. They would probably typically kind of shy away from anything like this. But if I think about biological safety, what about devices or software that changes the biology of the brain from a neurological standpoint, like AI, our different neurology. And if that doesn't fall, that's totally fine. It just popped into my head and I have no filter. I am kind of following you, Rowling, because this brain interfaces are so impressive for me. And because when we have software as a medical device and stand alone, software biological safety is not applicable at all to it. Why? Because by definition, related necessarily. But with things like social media, AI, all these different things, changing the way our brain is shaped. I think someday, if I look at the past of the FDA, for example, with CDRH, the Center for Devices and Radiological Health, that radiological history as to why they're over radiological is interesting. It wasn't just because of his medical devices, because there were radiological devices out there that were harming people. Maybe I'm getting on to a different subject. So let's get back to it. Let's come back to where we belong. I do want to know how you approach raw data analysis. You already mentioned some with those silver ions and so on. Is it different than how you approach data analysis in other fields? It sounds like you really draw from a lot of previous or a well of knowledge. Yes. Because I have my background in chemistry, it helps me a lot to understand what's going on here. Actually, you know, and have a look and understand, like, okay, I mean, basics, even there's a risk like polypropylene, but what type of polypropylene? Whether it's like mixture with something or like what are possible residuals in in this polymer, or if we are talking about some polymers, what was the reaction to produce a specific polymer? Was it like polymerization or polycondensation? Because there might be different residuals on it. And when I'm looking into this raw data, I'm really like sinking about it and describing it within my biological evaluation. Because again, it's very, very important to not be shy and ask questions, even if these questions are not very welcome, if I can, in this way. Okay. Yes. Well, I was just going to say, I would imagine a lot of people are looking for a pass fail. Just tell me if it passed or failed, but it sounds like it's a lot more nuanced. There's context. There's exactly exactly. And for me, it's exactly as a beauty of biological evaluation. Because you can just copy and paste some information from one biological evaluation to another. I know that it doesn't work in this way. Because again, we have to start from the very beginning, meaning from the intended use. We have to know our devices, like what materials are used, what disinfectants, what processes, et cetera, et cetera. And then we have to assess available information as well as test, available test results through this prism. So that's that's a beauty. That's why we always have a lot of fun here in this field. So yeah, I'm curious if you have any specific examples of when this wasn't done well. And maybe later on, you found out there were some biopic compatibility risks. I know we keep going back to the watch that causes a rash or something like that, but anything specific to the medical device field that you've seen that you're able to share. Yeah. I want to share the example from the bleeding edge by Netflix. Maybe you have seen this video. This movie, it was really, really great. And a friend of my anglina showed me this movie, and I was impressed. And really great examples that I would like to mention here is the issuer. issuer is a device for women contraception. And it was sold for a long time. And it was found out later by women that this device causes adverse effects, such as very different. So I just, yeah, even deaths. I mean, it was super like said. And unfortunately, so ladies provided say feedback, you know, like post-market surveillance, hello and complaints and all the things, but it didn't change anything. But in the end of the day, thankfully to their organization, because women just united, and they started to to be loud about this device. Okay. And in the end of the day, this device was cancelled from the production and actually sales. So here I would say that we have to be very cautious, especially with the devices that are implanted, or are used for a long, long period. Because look, one thing, I really loved this example. I had even a post on LinkedIn about it. For instance, I applied a tissue mask to my face. And when I get rid of it, I found out that I have allergy. Okay. Every scene was like red, red, and those things. So it's visible. It was like immediate. I just applied it through off. And here we go. Okay. But for long term, when, for instance, I used to work at the lab, and I worked with nickel solutions, and during the years, I have got sensitization because I have got allergy on nickel. But because I worked with it during a long time period, it accumulated my body. And that's why it was, I have got such kind of reaction. So what I'm trying to say is that we have to be especially attentive to the medical device with a long term contact duration. Because we can have some chemicals in our body accumulated because they are leaked from this medical device. And yeah, right now I'm really happy and excited to see that regulations and requirements to biological safety consider this aspect as well. And as I mentioned in the very beginning of a lot of discussion about what can I achieve. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. The examples of actual cases. I think that's really valuable. Yeah. I mean, you actually make me think of the accumulated exposure to what is it? I think latex gloves too. That can cause allergies as well. And I think there's something to think about. Yeah. There's lots. Yeah. Yeah. Yeah. Yeah. Yeah. We have to consider it. And as I mentioned in the very beginning with this infusion set, okay, they can be used for lifelong periods. So we have to consider it and all possible chemicals that can go through this bag as well as tube to the body. So that's important. I love the idea of thinking of it from the very, I don't know, the smallest component inside the device all the way to the time it gets thrown away. I look at that as kind of like the supply chain of your medical device. You know, I do I do a lot in design controls. So if you're designing a medical device, you have to design it to where you're you're thinking about, well, for example, maybe you have a device that a nurse is going to carry into a room. And it's sterilized. But maybe she opens it up, gets it already at her desk, puts it in her pocket, then goes to the room. It's that you've kind of defeated a little bit of the purpose here. So you had to think about all the way through. And so in the manufacturing, you mentioned a few examples there. I love that. One of them that's very common that I experienced as a manufacturing engineer was the mold release in a multi cavity injection mold. You know, they spray something on the mold so that it'll easily come out of the cavity. And that can cause problems. I think you already know where I'm going with that. So yeah, I think those are great examples. What you're the way you've described this, it makes me think of, you know, in the medical device industry, we talk about a risk-based, risk-based approach to everything. We like a risk-based approach. It feels like the focus is less in your mind, maybe less on what test do we run, and more what risks are we mitigating? Is that accurate? How would you describe it? Yeah, absolutely. Yes, because look, we have right now in the current version of Isocannones, Redish One, very well-known table, whereas the risk-like classification of medical device, I mean, as per biological safety, not like, for instance, medical device regulation, as well as these biological effects, like cytotexicity, irritation, synthesization, etc. But their case here might be that, for instance, there might be hazards that are not mentioned within this table, but just sinking and applying common sense, we can find out them. For instance, if medical device is applicable for adults, we need to think that also, for instance, pregnant women can use it until it's mentioned in confined occasions to this medical device. And from this perspective, we need to have a look and also consider developmental toxicity of this medical device, whereas as it would be any effects on pregnant women. So we have to apply common sense here. Surely, standard helps us with it, but it's not about testing. It's understanding what are specific hazards, associated with these specific medical devices produced within these specific processes, you know, and used as described within instruction for use. So we have to focus on it. Are you able to talk a little bit more about the risks associated with pregnant women? Because I feel like historically, we just don't have a lot of data on that. How do you go about evaluating that? Yeah, absolutely. Your absolute rights that, unfortunately, there is no, there is just a bit data regarding it. And for instance, when we found that, okay, we have to consider developmental toxicity, so we need to have a look into extractables and literables and the chemical characterization and these aspects, especially, and I'm highlighting it especially if we have a long-term content duration of this medical device visit passion. Because, again, talking about risk, we have to consider whether it's contact with intact skin, and here we have low risk or high risk if you're talking about the implants. Okay, it's like, first step, we where what we have to consider here. Secondly, if it's in plant-like high risk with a long-term contact duration, we need to have look into extractable literables. What are potential chemicals that could leak from the medical device? And I don't know whether I need to explain a bit the difference between extractables and literables. Please do. Yeah. Nietzschebles, if something that can leak in normal conditions, when we have 37 degrees C, if talking about European temperature, okay, so it's clinically relevant. What can potentially go in actual clinical, during actual clinical use? And when we are talking about extractables, we are talking about all possible chemicals that could go at all. And this is very strict approach and FDA, for instance, especially a lens tends to consider it. And here we are using conditions that are not clinical relevant, but for instance, elevated temperature, like 15 degrees C. Our body temperature is 36 degrees C, and 50 degrees C is like elevated temperature, you know? So, I mean, it's a bit too harsh, but okay. As well as like specific solvents, like hexane, for instance, not similar to blood. Blood, blood solution, that is like clinical relevant, but okay. So here, talking about extractable sentitubals, we have to analyze what are the chemicals that could potentially go from this medical device and assess, do perform toxicological risk assessment. And we have the value, it's called margin of safety. And we have to calculate and understand whether it's safe to use this medical device, for this audience or not, considering this margin of safety. I'm not a toxicologist, I'm just chemist who is doing biological evaluation, but it's like a very high level approach how to do it. There are a lot of drinks here because we have to consider uncertainty factors, also like no adverse, no adverse events, et cetera, et cetera, if it's like, ideally, prior level is normal. Yeah, no, that's great. I really appreciate you going to, especially the difference in extractables and leachables. I don't think I could have articulated it that well. So that was great. It makes sense. It sounds like, though, I could see a company looking at this and saying, okay, everything is over there. I'm going to take her the device, she's going to do her thing, then we're going to get back to business. You know, that's not really the way it should be, but I can see companies maybe treating biological safety or biocompatibility this way. And you can correct me if I'm wrong. What does it mean to impractical terms to really evaluate that or integrate that into your QMS or is it possible with design controls, player management, Kappa? Do you have any thoughts or opinions on that? Absolutely, yes. I also did a series of posts on LinkedIn and then biocompatibility is not a bubble and it must be integrated in the quality management system. Why? Because quite a lot of different events can trigger biological evaluation. For instance, changes in design, changes in materials. So here we go, here we have direct connection with change management process. Also, right now there is more and more emphasis on using post-market surveillance data because one thing is to evaluate medical device during design verification phase, you know. And another thing when the medical device is kind of test-rived on real patient in actual clinical use. So we have to consider this information and boom, here we have direct connection with post-market surveillance. Surely risk management because biological evaluation is based on risk management process. Okay. And now the thing you mentioned is about Kappa and here it also connected. Why? Because we can have some complaints that related to biological hazards, for instance. And in this way, we have to have a look into our biological safety and consider what is the risk here, whether it's low risk or high risk or moderate risk and also take some steps. Like, for instance, perform some additional investigation or, for instance, even perform some additional tests and if required, if we have this quite a lot of complaints related to, specifically to biological hazards, not like possible complaints, you know. So, yeah, biocomp is not a bubble and that's why I also said that biocompatibility is not just a science, it's about communication because we have to talk to each other and information should flow freely here because we need to know what's going on. And other things that I would like highlight separately is changes related to different regulations because we have to be aware. Like, for instance, Hertz and Agenic with Agenic Toxic Tour reproduction list has been updated with a specific chemical and we have to check whether our medical devices contain this chemical or not. And if they contain, we have to update our biological evaluation because we need to perform analysis, whether it's still safe or we need to do something with it, you know. And, yeah, so quite a lot of protections as you may see. Absolutely. I think every system within your QMS should know how the device touches the body and know how, you know, how the changes or the suggested changes would impact other people. I can just imagine we really hit on the watch. So let's go close. Let's say you have a medical device that's awareable. I don't know if some sort. And one person complains about it, itches or it, it's, it's, it caused a rash in me or something like that. I say, okay, well, you're just, you probably, I don't know if you write it off as the person is different than the rest of the population. That's not really helpful, but it could be an input into your risk management. Say, okay, maybe a few things need to be evaluated. Are there reactive versus proactive mindset shifts that could happen? And do you see? Well, let me kind of reel that back in. I can say a lot in a lot of different ways. I see companies that are reactive versus proactive. QMS is a good one. Cap is a good one. All of these can be examples of a reactive mindset versus a proactive mindset. What about with biocompatibility? Are there companies that you see doing it a lot better than others? And, and why? You know, I frankly believe that this publication of a new version of ISO 10 and S3-1, a lot of companies would forced to apply proactive approach. Why? Because a new revision of this ISO standard tells us that we have to assess biological safety throughout the life cycle of medical device. And even when we have just prototype phase, okay, we have to evaluate whether these materials are safe. And unfortunately, I can, I still can see that, it's rather, it's unfortunately, it's not still reactive, but we are going to it because look, we have changed this checkbox approaches. And right now, more and more companies are like, okay, it seems like we need to do some literature review. You know, and they are doing it. And they are having publications. And they are doing quite a lot of work related to biological evaluation as well as, but I still can feel that there is such kind of, you know, thinking that, okay, we just need to, to send this medical device sample to the lab, get some testing and it's okay. But no, it doesn't work in this way. You have to know your device and do some homework, at least, give the rinse in materials and analysis materials. But hopefully, hopefully, with this new revision, things would change. Yeah. Well, I'm looking forward to hearing more about that at some point here, but we don't have to go into that just at the moment. I know in the previous conversations, you've talked about how you train other, or train different teams at companies, cross-functional teams. How do you explain some of these complex biocompatibility aspects to those cross-functional teams, especially if they're non-technical? Are there things you going to with them? Yeah, there's great questions. Thank you very much for asking. I'm trying to use examples and trying to, yeah, so first of all, examples, like I provided this example of with allergy or what is the difference between irritation and sensitization? When I applied this tissue mask on my face, I have got allergy, like almost immediate allergy, so I have got irritation. And sensitization, when I worked in the lab with this nickel solution, during long time, I have got this reaction to nickel and I have got sensitization. So first of all, it's about examples. Secondly, I am explaining what's going on here and what is a goal. So why we are doing it or why is it required? For instance, some people are saying like, okay, we need citer, so we don't need to do irritation and sensitization. And I said, like, no, because we have to check different aspects of interaction with human body, because when we are talking about citer toxicity, we are talking about cells and cytotoxic effect, actually how cells react on it. So it's a bit different than other aspects. So I'm trying to use examples. I'm using simple words and I'm explaining why we need to do something or what is this concept in a very simple words as much as I could actually. I wonder if there's ever any, well, so when quality talks to marketing, for example, or sales, you know, and I don't know if you ever get that far down the path or upstream down to you, but how do you get that? Yeah, I imagine that there's going to be things, sometimes that you have to translate your speak into their language. It's just like when you're talking to a CEO, you have to have a different, maybe a different way of speaking. If I said something like this material could cause a release in chemicals that maybe causes inflammation, that might mean pain, complaints and recalls or bad publicity. Okay, now I start paying attention. Maybe I wasn't paying attention yet at pain or irritation, but complaints and recalls and bad PR, I can get that. If I'm not on the technical side or maybe I'm less empathetic of a person, I don't know. I don't want to throw anyone under the bus, but you know what I mean? There's always the economic drivers really speak loudly sometimes. So yeah, yeah, yeah, yeah, yeah, yeah, absolutely. I'm talking, for instance, to later affairs, we are talking about deadlines, about submissions, and if we don't start right now, you know, we will fail to meet this deadline and we will not get this document to your submission for your technical file. Man, you're good. Or for instance, for quality, if talking to quality, I'm talking like, okay, we have to do something with it. Otherwise, we have to stop production, because we have this complaint and we have to do finally with some. This is, you know, kind of, and yeah, I totally relate, but yeah, she's got pick one of the speed, cost, quality, you know, which way, yeah, yeah, yeah, yeah, yeah, yeah. We're going to impact something. Yep. Yeah, yeah, yeah. What advice do you have someone giving that, if someone came into the Medtech field or biocompatibility field, any advice that you would give to that person? Don't be shy and ask us the questions. Stay curious, meaning, and don't be afraid to go even deeper to understand the reason, to understand what you don't understand yet and communicate. Because I believe that communication is zikki here and we have to talk to each other as much as we can because information shelf low. Yeah, absolutely. And maybe that's the answer to the next question, but my last question I wanted to ask you was, if there's one takeaway that you give the audience or if you wanted them to take away from, what would that be? About communication communication. Hey, we had mentioned maybe a giveaway. Do we have something like that? I should have asked you before we started recording. We'll talk about it afterwards. Those are listening. Just assume we do and go check the show notes so at least you can maybe get something from Marina. We'll see what we can, what we have if we do. Maybe we didn't talk about it. So if we didn't forgive me. So let's, yeah. All good, all good. Marina, this is great. Anything we missed or you feel like you want to just touch on one more time. No, I believe that's it. I just have a question that we can discuss it after the day. It's so smooth. I love it. Yeah, it was so good. Talk to you. Thank you so much. Really appreciate you sharing all this information. And I'm looking forward to the webinar in a few months. And I hope those of you listening are able to attend. It's a chance where you can ask questions directly. We always have the option for you to do that. And even if we don't get all the questions, we forward them onto the presenters. So maybe Marina is able to interact a little bit as well. And I will also say follow her on LinkedIn because she is very active and very educational and entertaining. And I just, it just, it clearly shows that you care about what you're doing. And I think that's really valuable. Oh, thank you so much. And I'm here very happy to be here and enjoy our conversation. And please everyone join our webinar in a few months. It would be a lot of fun. Awesome. All right. We'll let you all get back to the rest of your day until next time. Take here. Thanks for tuning into the Global Medical Device podcast. 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