Name: Combination Products in Europe: Navigating Pharma, Devices, and MDR Expectations
Uploaded: 2026-09-25T15:16:07.201Z
Duration: 50 min 47 s
Description: Combination Products in Europe: Navigating Pharma, Devices, and MDR Expectations

Transcript for "Combination Products in Europe: Navigating Pharma, Devices, and MDR Expectations": Hello, and welcome. And thank you for joining us today. We're here to talk about combination products with a focus on the European regulatory landscape. And more specifically, where companies tend to struggle when trying to bring these products to market. I'm Brian Cleary from NSF Life Sciences, and I'll be facilitating today's discussion. Now you probably already know what a combination product is, and you may be working with them, you may be developing them, or actively trying to get them improved. So today's session isn't a beginner session or as our American colleagues often would call it, a combination products one zero one. It's really about what makes them hard in practice where pharma and device requirements collide and where timelines can sometimes get misaligned. And also, it's about regulatory surprises that often can pop up very late in the day. So I'm joined by two of our experts who work with combination products all of the time. Firstly, I'm joined by Maria Callahan who is a senior consultant in our pharmaceutical business like myself. Marie is based in Ireland, and Marie brings deep experience from the pharma development and regulatory side. And also, moin moin, as they say in Hamburg, in my colleague, Suzanne Veps, who is a senior consultant for our medical devices business based in Hamburg, Germany. And Susanne specializes in MDR usability and device compliance, particularly for combination, or as we often call them, combo products. And together, they represent both sides of the equation. So we've got pharma side and we've got the device side. Marie, let's start, if you don't mind, with a a brief introduction. Give us a bit of background on your expertise and your experience. Yeah. Thanks, Brian. And as you've already mentioned, my name is Maria Callaghan. And I have worked in the pharmaceutical industry for over thirty years across r and d, quality control, regulatory affairs, quality assurance, supplier quality management, and as a qualified person. My first job was actually in combination products and inhalations, but at the time, it was so long ago, they weren't even called combination products at the time. It was a pharmaceutical that had a delivery device with it, and that's all I knew about it. But after that, it has been pharmaceuticals all the way for me. So most of my career has been in complex pharmaceuticals and biotech products. So I spent my time helping companies navigate the practical challenges of development, compliance, and bringing pharmaceutical products to the market. And what does interest me about combination products is that they sit right in the middle between two really regulated worlds, which creates opportunities and, as we're discussing today, challenges. Okay. And, Susanne, same question to you. Give us a bit of background on your expertise. Mhmm. Yes. So my name is Susanne Neves, and I'm a senior consultant specializing in medical advices with a strong focus on combination products and also the overall MDR compliance. So, yeah, I originally studied pharmaceutical biotechnology and spent a few years working in the pharmaceutical industry industry before moving to the medical device space. And I'm based in in the Hamburg office in Germany where NSF has a strong focus on just medical devices. So, yeah, I'm specialized also in areas like the process validation, clinical evaluations, and studies, and as well as post market surveillance for medical devices. And, yeah, now I really enjoy helping companies bring the device and pharma words together, especially when it comes to usability, design process, or regulatory strategy. Okay. Thanks very much to you both. Marie, I'm gonna start with you from a pharma perspective, if you don't mind. Why Why are combination products such a hot topic right now, particularly in The EU? Well, I suppose from a pharmaceutical perspective, the main driver is the increasing use of advanced therapies. I mean, there are new biologics and targeted treatments being developed all of the time. And those therapies, they can't be administered in just a simple way anymore. They require dedicated delivery systems such as auto injectors, pens, or inhalation devices that I mentioned already. And we're also seeing such huge innovation in drug delivery itself and patient centric solutions, connected devices, and even software and apps that are are used during during drug administration. And as a result, what used to be a stand alone drug is now frequently part of the combined drug delivery system that makes them more common across the industry. Suzanne, let's look at this from the other side of the of the equation from the device side. What are you seeing from devices and particularly in in the regulatory side for, drug combination... Drug device combination products? Yeah. So, actually, we are seeing a quite big regulatory shift in the European Union. So with the MDR, the expectations from the device part had really gone up. So what used to be is more of a simple delivery system, or sometimes even just packaging is now treated like... Or, yeah, more like a full medical device with all the expectations around design, usability, risk management, and also clinical evidence. So this becomes more relevant as devices themselves are getting more sophisticated. So especially with the digital features and software supporting the drug delivery. So, yeah, there are more, there is a... Yeah. As I already mentioned, a big regulatory shift, and companies are really dealing with several things at once. So there are more complex therapies, more innovative and connected delivery systems, And I think that's why combination products are such a hot topic. Okay. So we've got the complexity that Marie and yourself have mentioned. But from a... From device side, back to you, Suzanne, on this. Is the challenge more about the new rules, or is it about how the rules are applied in practice? Yeah. Maybe I can stay in because that's a really great question. And, yeah, in reality, it's a bit of both. So the new roots under MDR have definitely raised the bar. Requirements around design controls, usability, and documentation are more detailed than before. Yeah, in practice, as I already mentioned, there is a bigger challenge is there are rules which should be applied. Companies are not always use... Thinking in a in a device way. So, for example, in terms of usability engineering or structured design processes. So, yeah, I think the expectations from the notified bodies also can vary. And there's still a degree of interpretation involved, So this creates uncertainty, I would say, especially for pharma teams who are more familiar with the clear regulatory pathways. So, I would say it's not just understanding the rule. It's about the implementation, implementing them, yeah, effectively in practice. Okay. So when you put that together, we have more complex therapies, more device dependent delivery, and there's actually higher expectations as well for the device component, and they're all coming together at once. So what I want to look at is what this means for companies in practice because a lot of people from different companies of different different shapes and sizes essentially are joining us on on the webinar today, or the roundtable. So let's make it practical. What does the increased complexity actually mean for companies trying to get these products approved? And, Marie, I'm gonna start with you. So, you know, look look at the... What does the increased complexity mean for them? Well, so in practice for pharma teams, it means that developing a combination product isn't just an extension of the drug product. The device is no longer just for delivery. Companies need to manage two different development logics at the same time, the pharmaceutical and the device, and ensure they come together in a fully aligned way when you're submitting. And how I've explained this when I've been doing some training on combination products is that, you know, pharmaceutical regulations grew up around medicines and the chemistry world and devices was more of an an engineering world. And they all were developed to do the same thing to create a safe effective product but using different terminology, different methodologies. And now when you've got a combination product, you've got really good regulations on both sides, but you've got to meet both of them. So from a pharma side, we're used to focusing on things like the quality, the stability, clinical performance, and regulatory approval. But now considering things like device design controls, usability, risk management, and notify body expectations, you need to anticipate those material. And even the whole notion of a notified body would be something totally alien to someone who has always worked in in pharmaceuticals. So that makes it challenging. And what... The other thing that makes it challenging is that decisions on either side, changes on either side may impact additional studies or additional regulatory assessment on the other side. So really, timelines are not as straightforward as as what you would be used to for pharmaceutical people. Yeah. I know that's something we touched on in in the introduction today. So, Susan, I'm gonna ask you the the very same question about the increased complexity, for companies on the device side. What do what do you see? Yeah. So I can bring an example. So when we see... What we've seen in practice is, for example, with an auto injector, Yeah. It was originally considered straightforward. Basically, an established platform device with only small modifications because it was only, yeah, already marketed under MDD. And the early on, the assumption was the device is problem. Yeah. So this should be just a major... This shouldn't be a major topic. But then, but, yeah, but when usability studies were actually conducted, especially with the change of the intended user group, for example, now it will be more older patients, it turned out that there was a real issue. So some patients had difficulties, activating the device. Other do... Others, didn't hold it long enough to deliver the full dose or misunderstood the feedback of the device. So, yeah, under NDR, you may need to demonstrate that the device can be used safely and effectively by all of the users you defined already in the intended user population, and this could be ignored. And, sometimes, or so something that initially seemed low effort suddenly turned into a major work stream, even late in development. And that's exactly the kind of situation where things become very, very time consuming. Okay. You've actually anticipated my next question, which was about things appearing easy at the start of the project Yeah. Were becoming more, I think the the phrase I'd use would be painful later on. Let's let's look at the the EU specifically, because I know you've touched on MDD and then its its successor, MDR. Suzanne, I mean, how are combination products regulated in the EU today? And what do companies need to get right on this? Yes. So in the European Union, the combo products aren't regulated under one single framework. It really depends on the primary mode of action. If it's physical, immunological. So in most cases, especially for drug device combinations, they are handled as medicinal products, but the device part still has to meet the MDR requirements. And that's, where things get very tricky because... Or... Yeah. Even though you're going through a pharma pathway, you still need to show that the device meet the relevant safety and performance objectives, the requirements. And a key aspect here is the MDR article 117. And, for certain products, yeah, you need a notified audio opinion confirming that the device complies with MDR and has to be part of your submission. So in practice, that means you need proper device documentation, ready, yeah, covering design, performance, risk management, and all... And and... Sorry. At the same time, you also need a pharma dossier. And, yeah, I think the biggest challenge here is the timing. You need to engage the notified body and, yeah, while making sure that your drug and your device development stay aligned. Yeah. I just wanted to, to drill down for a second on the notified body piece because notified bodies were in the news quite a lot a few years ago because with the changeover from MDD as a directive into the regulation with MDR, there was, you know, well publicized shortage of notified bodies. So they would have been brought to people's attention more than they previously had been. With regards to companies for drug devices now, what do they typically get wrong or underestimate about their interactions with the new clients? Yeah. That's a really good question because, I think a lot of companies really underestimate how early and how structured that interaction needs to be. So what we often see is that companies treat the notified body more as a final checkpoint, something they engage with, yeah, close... Just close to submission. But in reality, the expectations are much higher. So the level of detail they are looking, can be quite significant. Another thing that's often underestimated is that the notified body is not just checking whether the device works. They're really looking how everything is documented and how the, interaction is documented and con... Yeah. And connected. So things like traceability, risk management, justification, and design decision becomes very important. And, yeah, I would say in my experience that the notified bodies can have very different expectations and, can... It can come to a surprise, especially for pharma teams that are used to have more standardized or, yeah, standardized processes. So that that actually leads me on, perfectly, some might say, to my next question in terms of the distinction between what pharma companies think the process is going to be like and what it's actually like in real life with a notified body. So what does good enough device documentation look like in theory versus what, a major notified body one might actually expect? Yes. So the gap between good enough and what notified bodies actually expect is often bigger than expected. So, in theory, companies often think in a more pharma driven way. So good enough means the device works, delivers the back, and, the main performance tests are in place. So that's, yeah, the part of the overall product. But, the combination... Especially for combination products, notified bodies are looking at the device more independently. They expect, yeah, let's say the same level of structured documentation as for the stand alone device. But, yeah, they want to see a clear traceable link from the user requirement to design inputs, to risks, to verification and validation for all the device part. And the issue is not that the data is missing, but that it's not organized and justified as a complete device development story, especially when you're consider... Considering the combination product. So for pharma, good enough is often about showing the product works as a whole. But for notified bodies, it's about demonstrating that the device component on its own has been developed in a full controlled traceable way under the MDR requirements. Marie, I'm not gonna turn this into a courtroom scenario, and ask you to defend the pharmaceutical industry. But how does it play out from a pharmaceutical side? Well, from the pharma side, the data probably does exist. And I think, you know, there's so much data developed through it at a a life cycle of pharmaceuticals. But it's not always generated or organized or connected in the way that the notified body is expecting. And so in in pharma, we're very used to building a regulatory story around quality, safety, and efficacy. But again, they're through a different lens than the device. With the combination product, as Suzanne has said, you need that clear device development story as well. And it's not always thought about in in a pharma context. And Suzanne is right when she says that oftentimes, the notified body, part of it is seen in the pharma life cycle as being just that final check. But then, you know, as I said, the data and the science is there. We're getting it from those different systems and shaping it in a way that the notified bodies expect or will recognize as being support. You know, that if the if the pharmaceutical company is developing a combination device, they will make sure that it's usable, that it's designed properly, all of that. But they will be doing it with that pharma lens so it won't be organized in the way a notified body will accept it. And that's where they often discover they need a much more integrated approach than they originally anticipated. Suzanne, if I can ask you then, in terms of... At a pharmaceutical company Mhmm. Someone has to own the device strategy. Or so who should own the device strategy? That's my that's my question to you. Mhmm. Yeah. So in combination products, that ownership is often not clearly defined, and that's exactly where the problem starts. So in many organizations, the device doesn't really belong to one function. Pharma teams focus on the drug. Engineering teams focus on the device. And, yeah, the regulatory sits somewhere in between, and, I would say the device strategy can end end up beginning or being a bit fragmented. So, ideally, you should be... Yeah. There should be a clear ownership of an integrated product strategy, someone or a team that understands both. So the pharma and the device requirements and can bring those both perspectives together. So, yeah, because the reality is the decisions on the device side, like design usability or supplier choices, even... Yeah. Even supplier choices can directly impact the overall regulatory pathway and the submission. So if no one really owning that end to end view, You often get late surprises and, yeah, misalignment in timelines, gaps in documentation, challenges with the notified bodies. So there should be somebody who has the expertise of both sides to have the overall view of both perspectives. It's interesting you touched on that, Suzanne, because I'm gonna come to Marie next because I want to to look at the issue of mindset, of the pharma mindset versus the device the device mindset because you you mentioned two two words that I just jotted down here, fragmentation and decisions. And in terms of, the fragmentation piece, Marie, from a pharma perspective, can you tell me what fundamentally drives the development decisions in a pharma plant? On a... So... Yeah. Okay. So in in pharma, development decisions are typically driven by patient safety, clinical efficacy, product quality, and stability. And ultimately, we're trying to to demonstrate that the product consistently delivers the intended therapeutic benefit throughout its life cycle from development through to commercial use. And we tend to work with fairly well established development pathways. There's a strong emphasis on generating robust scientific data, managing risks through a structured regulatory framework, and making sure that any changes are are supported by appropriate evidence. So as a result, it's often very influenced by your clinical outcomes, your stability data, your manufacturing robustness, and the potential impact on your filing the timelines. So what key elements like formulation, dose, or clinical strategy are established, there's usually a strong focus on maintaining consistency and avoiding unnecessary changes. Because any changes at that point, once you've tied down your formulation and dose, any changes could send you back into redoing clinical or stability or something like that. So that's why combination products can be challenging because the drug is following this fairly predictable known pathway. While the device is still evolving through its usability studies, design iterations, and user feedback, so the device can be changed and that can actually cause an an issue with the drugs needing to be changed as well. So bringing these two approaches together requires different mindsets and closer collaboration than I think pharma companies have traditionally been used to. You know, that... You know, it might be the right thing to do to make a change to the formulation, but that's a bigger job than maybe the device developers appreciate. Okay. Suzanne, I'm gonna come back to you on this as well. So we've we've got the pharma perspective here. So what... What's the device comparison or the device perspective on this issue? Yeah. So I would say it's quite a different mindset in the device world. As Marie already mentioned, so the development in pharma side often follows a more structured path with a strong focus on clinical efficacy efficacy, safety, stability. And in the device world, you all may... Mainly start with the user needs, translate them into design requirements, build and test, learn from the results, and then you can refine the design. So it's less of a straight line, and then it's more a learning loop. And a good example would be a wearable drug delivery device, so like an on body injector or a patch pump. So at first, the main question might seem quite simple. So does the device deliver the drug deal correctly over a defined period of time? But in but in reality, we have questions like, does the... Or does the adhesive stay in place during normal daily activities? Does the device still perform reliably? If the patient moves, sweats, or wears, for several hours? So these are typical device questions, and they often lead to design changes. Marie also mentioned this, example. So when the designs change... The device, design changes, so there's also additional testing during development needed. And that's why usability, performance testing, risk management are also central in the device world. And compared to pharma, the device mindset, yeah, it's more about testing, learning, and refining. Suzanne, you talk about mindset, and I just just wrote that word down. And be be nice to each other because one is on the pharma side, one is on the device side. Where do you see the... I'll ask you first. Where do you see the two mindsets colliding? Because we've got chemist in our area. Yeah. So they most often collide at the point where pharma wants to lock things down, but the device side is still learning from testing. So, again, an example, or as I mentioned before, the OnBody injector. So from a pharma perspective, the product strategy and submission timeline may already be fixed, but then the usability study shows that the patients misunderstand the feedback signal, remove the device too early, or are unsure whether the full dose, has been delivered. So, yeah, another very common area area is the drug, device compatibility. So for example, a biologic might interact with the container closure system, the syringe barrel, or other materials in the delivery system. So we have to consider the compatibility of everything. And from the device side, the component may be standard or even, yeah, well established. But on the pharma side, the question is, does it affect the stability of the drug, the aggregation, the dose accuracy, or product quality, or the shelf life? So we have different questions in mind. And, yeah, as we already mentioned, there's a different pathway, a different perspective we need to follow. Okay. Marie, what would you say to that? I would I would say, I would concur with Suzanne that the the challenge does come around change. And as as we've mentioned, when... Once something is tied down in format, changing it is a big deal. So if the device has a change in it that could potentially impact or you need data to prove it doesn't, clinical data, stability data, b testing data all takes a lot of time and it's really only built into your timeline to complete it once. So the so the the plan or the the idea that you would have to turn around and redo part of your clinical study or redo stability, you know, you can't get six months accelerated stability any faster than six months. That's that's just the... That's how it is. And so you have your your strategy is that you're going to develop this product with this device. You're going to submit it by this date and you will be commercial by by that date out in the future. And that has all of your clinical built in and your stability studies and everything. And then for a device to have a change in it, that could potentially impact on any of those studies that you might have to repeat some of those studies. That's where the big challenge will come in. Okay. So we... We've talked a lot about the differences and the clashes and the mindsets and the fragmentations. Let's look at the positives in terms of collaboration. Suzanne, how do the differences you talked about show up in in the real projects that you see with your clients on a day to day basis? So you mean differences in the real projects? Or... How how do the differences between the engineers and the chemists show up in real projects? Yes. So you see it, very quickly in the day to day discussions. So take a prefilled syringe, for example. For example, the pharma is usually looking at things like, is the drug stable, container closure okay, do we have the right quality data, and the device team looks at the same syringe and asks, yeah, asks slightly different questions as, yeah, how much. Force, does the patient need to push the plunger? Does the needle safely feature work reliably? Does everything still perform after storage? So it's the same product, but people are looking, it with different lenses. Okay. Marie, sorry. I'm sorry to cut across. Marie, does that match what you see in the pharma side of the business? Absolutely. And everyone on both sides, and there shouldn't really be sides because there's only one product. Everyone's working hard and making progress, but they're often often measuring success differently. I've seen situations where pharma think we're ready to go. The product's nearly there. The drug package is strong. We've got our stability. We've got our clinical. You know, we're we're we're almost there. All our quality data is in place. And at the same time, the device team are still working through their design, still tweaking, through their usability studies, risk management activities, and design verifications or managing those notify body expectations. So they genuinely all feel they're on track, but they're looking at readiness through different lenses. So what happens is that that really only becomes visible when people start preparing the submission and putting everything into regular fares and then trying to bring everything together into one integrated product story and that's where the gaps become, visible. It gaps in documentation, gaps in timelines, responsibilities are are gaps in evidence. And that's why alignment is really critical and not just alignment on the timeline, but alignment on on what ready means. The most successful projects are the ones where those conversations happen really early and where pharma device regulatory and quality teams are working towards a shared definition of success rather than looking at a shared date in the calendar. You know, just everybody making sure that they they understand the end goal is to create a product that is really submissive... Ready for submission and not not just a list of to do... A a a to do list. It needs to be implemented. I I want to look... One of the issues, I suppose, when I think... And I'm not a scientist here. But when I look at, a drug device product, I think of the complexity of it. I think of some of the products we use here as a family or people that I know have used. Suzanne, just in terms of of... From your side of of the business, where do companies underestimate the complexity of these products? I would say everywhere. I think companies often underestimate the complexity exactly at the points where the drug and the device come together. And, yeah, let's say the drug may be well understood and the device may also be based on an established technology, but the combination still needs to be proven as one integrated product. So finally, companies often underestimate how early of this, yeah, this needs to start if the device is treated as something that can be added at the end. It usually became painful later. So you have to, yeah, have to look or, to, concentrate on the integration right at the beginning. Yeah. Let... Let's look at the the issue of integration because I'm assuming you've got device and you've got pharmaceutical documentation here. Marie, what would you say about the complexity issue about where do you see the the pharmaceutical businesses encountering complexity here? What I often see and and from my own experience of working in a pharmaceutical company that did start making combination products is underestimating the effort required to integrate the device requirements into the overall pharmaceutical program. So the science behind the drug is well understood. And the device might even be based on an established platform and a syringe, for example. Lots of syringes out there and they're... So they're very well understood. But bringing the two together as a single product is where you build your complexity and it's not just the technical aspects. Companies need to coordinate the documentation, the development, the suppliers, the timelines, the quality systems and the regulatory expectations across both domains. And as I've mentioned, decisions on one side can have a consequence for the other. So maintaining alignment throughout the cycle becomes increasingly important as the program progresses. Because what can look quite manageable at the start can quickly become complicated when you're dealing with different teams, different regulatory requirements, and ultimately the need to build one coherent product story at submission. And that's where companies realize that combination products require a much more integrated approach than they originally expected. Just on that, that reminds me of a project worked on with a company many, many years ago where it was the combination to use... I know it's upon here, of the device and drug mindsets and and working practices in... Into the approval piece. And that's where they came up against a lot of problems and and brought us in. Just, Marie, in terms of the approval risks that you see, what do you think the biggest approval risks are from a pharmaceutical side, on on getting a drug device combination product across the line? It's not usually the scientific stuff because the engineers on one side and the scientists on the other side are often really good at getting their data together. It's more often the gaps in that integration where they don't fully align, where changes haven't been assessed across both components, or where key regulatory expectations are identified too late. I mentioned earlier, pharmaceutical companies are not not familiar with the notified body pathway. So notifying the notified body too late is often one of those issues that can create significant delays. Suzanne, what would you say in terms of the the device side? Yeah. I would go with it. So the biggest approval risks, I see are often not huge surprises around the drug itself. It's more that the d... Or, yeah, that device related gaps show up too late. On a... One example is the documentation. Also, Marie already mentioned it. Teams may feel to have all the reports, but when reviewers look at it, the story isn't always clear. So why was the device designed this way? What risks were identified? How were they controlled? And, yeah, I would also say another big, big one is, again, the usability. So if patients or health care professionals use the device, you need solid evidence that they can use it safely and, very important, also correctly. And if that evidence comes late or doesn't match to the final design, it become very painful very quickly. And, yeah, also, Marie already mentioned the notified body, and I want to emphasize the notified body interaction since... Or... Yeah. Because companies often underestimate how much time that can take, especially if questions come back or documentation isn't fully major. Yeah. So I would, yeah, highlight or, yeah, emphasize that late changes are always risky. Something like, may look like a small device change, a component, or a material change. It can be very significant for combination products and can be a trigger for a lot of follow-up questions and around performance stability, compatibility, and everything from the notified parties. That that actually leads me on to a question I wanted to ask is that when do companies usually realize that there's a problem? Suzanne, do you wanna pick this one up first? Yeah. I would say, every time when there are late device changes. So something, as I mentioned, component material can look like... Can look small first, but, in a combination product, it can raise questions. And if that comes late, rarely, it's rarely a quick fix. So it can mean more testing, updated documentation. Yeah. And Marie Marie from a pharma side, Suzanne talked about, you know, changes in materials or components. What about the pharma side? Well, anything that involves creating extra data is going to cause a a delay and upset and panic. But from my experience, it's often very late in the day when people find out that they have gaps is when they're attending the final submission package. Up until that point, both work streams attempt to be working in in parallel rather than together and progressing quite successfully and individually or in good shape. But when everything needs to come together in that... Into that single regulatory story, that's where you see your gaps in strategy or documentation or ownership or alignment. And at that stage, you discover that there were assumptions that were never fully challenged or interfaces between the drug and the device that haven't been addressed as thoroughly as expected. So rarely one major issue is often the accumulation of smaller gaps that only become apparent when you're trying to demonstrate that the combination product works as one integrated system and is supported by a complete cons... Consistent submission package. Like I said, everybody is doing their their best to have have everything, and all the information is probably there. It's just getting it into that, into that expected model for both notified body and a a regulator. Okay. I I wanna move on, and to to quote an an old boss of mine from a long time ago. Don't bring me problems. Bring me solutions. So, Suzanne, from from a device perspective, what does a strong, well produced combination product strategy actually look like? So I would say it starts with the early integration, meaning the device is not treated as a separate work stream. It needs to be built into one overall product strategy from the start with proper design controls, clear user and device requirements, and, yeah, of course, a strong link to the risk management. And, again, the usability is also a key because for many combination products, the patient is part of how the therapy is delivered. So you need to show that the device can be used, safely in the real life. And, of course, the whole device approach needs to be aligned with m d... MDR expectations, including the documentation, evidence needed, incorporating the maybe CTD format. And in short, yeah, we need one product story from the beginning rather than trying to bring the pieces together at the end. Marie, what do you say to the pharma side of this? Well, I would I would totally agree that early early integration as as early as possible is is key. But the one thing I would say the reason this hasn't been the case is that oftentimes, particularly something like an injectable, has been developed as an injectable and not as a combination product at the start. So you have a very strong drug package already. And then there's a a move from having it as a standalone vial to making it maybe something in a prefilled syringe. And so the fact that it is now going to be a combination product is almost missed. It's just it's all... It's not designed originally as a combination product. So I think recognizing when you have a combination product or when it is becoming a combination product is really important. And to understand the nuances behind that that it's not just a different delivery device for the same product, it is a different product type. And I think once people understand that different product type, then that integration becomes more natural. I I hope that makes sense. But it's it's just sometimes in in my experience, the pharmaceutical has the next the next generation of the product becomes a a combination device. And the impact... Implications of that are sometimes missed until it's too late. Okay. I know we're, looking at the at the clock now. We need to wrap things up in the next few minutes. I'm gonna look at one or two final questions, if you don't mind. Suzanne, I'm gonna start with you. So if an experienced company is already developing a combination product today, can you tell me can you tell me one thing they should reassess right now? So even companies or experienced companies should reassess whether the Dragon device still work together as one system, not just whether each part works individually. So, that means, looking at looking at compatibility, stability, dose accuracy, device performance, shelf life, and so on. Everything what is, yeah, MDR relevant should be reassessed since we have now the new regulations. We have an EMA task force now, especially for combination products in The EU. There is bigger focus now on the article 117. So I think every... Also every pharma company, should now reassess if the device requirements are covered. Okay. Marie, from a pharma perspective then, let's say, pharma company x y zed limited, whatever we want to call them, is developing their combination products. What do you think is the one thing they should reassess? I think change management. Because over the life of any program, there'll be changes to formulations, suppliers, materials, processes, and devices. And the companies where this falls down is assessing any change only on the parts that's being changed, whether it's a device change or a a, pharmaceutical change. And they really need to look at the interfaces and do their change management across the entire unit, see this combination product for what it is, an actual independent product. It's not a pharmaceutical. It's not a device. It's a combination product. And so understand how the changes impact the the whole product and that will make things, this will force the integration a little bit more. Okay. So a final topic before we close. Marie, for you, looking at your expertise and your experience in the the drug device combination world over over many years, at what point in the development of a product do companies most often realize that they actually need outsizer... Outside help? Often, it's when they're preparing their submission and they suddenly see the drug and the device story doesn't fully connect around requirements, risks, testing, or documentation. Or before or during the notified body interaction particularly for pharma. I definitely underestimated the notified body interaction when I started out in combination products. And that's when teams realized they're not completely sure what level of detail will be expected for the device part because they haven't been dealing with devices. They haven't been dealing with notified bodies. So it's a completely new entity to them. And often, it happens after a change, a new device component, a new supplier, even a formulation change when they need to understand what the impact is on the overall combination product. So it's not that any company lacks expertise. It's more they need an independent view to pressure test their strategy, identify gaps, and make sure that combination product package is a strong... Is strong enough before it goes into review. And what what would you say to that, Suzanne? I would go with it. So, yeah. It's, yeah, it's not because of the lack of expertise. It's because they need a separate independent view of everything. On the complete strategy to... As Marie already mentioned, the gaps. Is the combination product package strong enough and... Yeah. So, the best, yeah, the best is not to come to us just be... Prior submission. It's, right at the beginning from the development planning until the, yeah, pro... Complete project management, so we can have everywhere. Okay. So let... Let's wrap up. Can I ask you both to give us one key takeaway? So we've been here forty, forty five minutes. We've got the whole world of drug devices. What what is the one takeaway you would you would talk to the audience today about? Marie, do you wanna go first? Well, my key takeaway would be that... To treat the combination products like an integrated product and stop thinking of it in terms of pharma side and device side, but it is an integrated product. And then the earlier that you align the science and the development activities and the regulatory strategy, the fewer surprises that you will face later. But see it as... Stop seeing it as one side arguing against the other. It's one integrated product. Okay. Suzanne, what's your takeaway? Yeah. Don't treat the device as an add on combination product. So the drug and the device need to be developed, developed, assessed, and, justified as one integrated product. And, yeah, that means understanding the interfaces early, especially around device interaction, usability, risk management, and MDR expectation would help a lot. Okay. Thank you both for the insights. Really appreciate your time today, and thanks to everyone who joined us today. I say "Slán" to my colleague in Ireland, Maria Callaghan, and "Tschüss" Suzanne in Hamburg in Germany. If you'd like to continue the conversation or explore how these challenges apply to your own programs, contact us at NSF Life Sciences. You can contact us by email, and that email is lifesciences@nsf.org. That's lifesciences@nsf.org. Thanks again, and goodbye for now.