Charting The Waters Of Drug Delivery Innovation With Suttons Creek

In this episode of In Combination, the technical leadership team from device consultancy Suttons Creek joins host Tom von Gunden to discuss trends in the patient landscape driving innovation in drug delivery, including combination products and therapies. The conversation covers patient self-administration, emerging modalities, and key considerations in product development, regulatory pathways, and the supply chain.

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Episode Transcript

Tom von Gunden, Chief Editor, Drug Delivery Leader:

Welcome to another episode of In Combination. My name is Tom von Gunden, Chief Editor at Drug Delivery Leader. And for today’s In Combination episode, I'm pleased to introduce folks who you may see on additional episodes down the road. And these are folks from the technical leadership team at Suttons Creek, which provides consultancy services around devices and combination products to the biopharma industry.

So, first we'll learn who is all on the call from the team. And I invite each of you to give us a little bit of perspective on where you have been in your career in the industry, what brought you to Suttons Creek, and how those experiences, either prior to Suttons Creek or at Suttons Creek, may inform the kinds of perspectives and insights that we hear from you today and potentially down the road.

So, for that, I'm going to start with you, Jonathan. If you could introduce yourself and give us a little —background and insight into who you are and how you got here.

Johnathan Amaya-Hodges, Consulting Director, Suttons Creek:

Sure, Tom. Thanks for having me and us today. Looking forward to the discussion. I'm Jonathan Amaya-Hodges, consulting director at Suttons Creek. Been here four years. Prior to that, through my now 20-year career, been at stops at a biotech pharma company working on quality and regulatory for combination products drug delivery devices. And, related, did a stint at an in vitro diagnostics company. And then served my career at a big pharma device company working in combination products drug delivery. So, [I] certainly follow what you are doing and [am] interested in chatting here today.

Well, welcome. Glad to have you; it’s my pleasure. Whoever wants to jump in next, feel free.

Konrad Walzer, Director, Technical Services, Suttons Creek:

I'm Konrad Walzer, director of technical services here at Suttons Creek. I'm a new person here, a new hire. But prior to that, I've got 30 years’ experience at large organizations — Becton Dickinson, CareFusion, Hospira, Baxter Healthcare — in various capacities in technical engineering roles: platform development, supporting drug-device combination products, infusion pumps, and complex systems.

Excited to have that talk.

Me too, so am I. Welcome, Konrad.

Albana Thorpe, Director, Technical Services, Suttons Creek:

Well, Tom, thanks for having us. My name is Albana Thorpe, technical director here at Suttons Creek. I've been here for about a year. Prior to that, for the last 17 or so years, been in implantables, combination products, device manufacturing. My main area of expertise has been device manufacturing — large, development programs where we partner with pharma and get a combination product out. So, I'm excited to be here and excited for the discussion.

Well, welcome.

Bryan Bobo, Associate Technical Director, Suttons Creek:

I'll go next. My name is Brian Bobo. I'm an associate technical director here at Suttons Creek. I've been with Suttons Creek for coming up on, I think, about two and a half years. Before that, I spent about nine years at Regeneron Pharmaceuticals in the combination product space. So, I'm an engineer by education, so I have worked in roles starting in more core engineering activities focused on primary container development. And then later in my career have tended to shift more into a lot of program leadership roles, focused on everything from your standard ophthalmic syringes to auto injectors to on-body systems.

So, I consider myself more of a generalist and kind of helping lead some of those systems engineering programs, getting everyone moving in the right direction.

Good to have you here. Thanks.

Carolyn Dorgan, Director, Technical Services, Suttons Creek:

I guess I will wrap things up. I'm Carolyn Dorgan. I'm one of the other directors at Suttons Creek. I've been here about three and a half years, coming up on the four-year tenure, like Jonathan. Prior to Suttons Creek, I was at the Food and Drug Administration, where I was in the injection, infusion, general hospital, human factors team, led a lot of the combination product reviews, managed the team, part of the initiatives, develop the processes and working across centers, several standards and guidance documents, both in the pre- and post-market space.

Prior to that, I was an R&D quality at a number of medical device firms, working in pediatric device delivery specifically. So really interested in the patient perspective and getting therapeutics to special populations. So, I’m an engineer by training and I have a business degree along the way. So really excited to dive into some of these topics and, really, work with the industry to get therapeutics to the patients who need them.

Well, thanks. Welcome, Carolyn.

I'm going to pick right up on one of the concepts that you introduced right there at the end. And that's the patient landscape and the therapeutic needs out there. We'll make our way through a conversation that moves into the biopharma organizations and out into further areas of the industry. But let's start with that patient landscape.

So, as you folks look out over that landscape, toward patient needs and trends and therapeutic targets, what are you seeing? What's most notable and most in front of you these days?

Amaya-Hodges: I'll go first, but I'm sure the rest of our team will have other thoughts after that, too. I think it's clear, I think even more so than it has been in the prior decade or so, that home self-administration of therapeutics is critical. Look at the GLP-1 space and the number of pens, autoinjectors, etc. associated with that that are pretty prevalent in the general population beyond what we've traditionally seen in smaller segments — rheumatoid arthritis and rare diseases and things like that —where there have been biologic injectables that have been pretty continuously coming to market.

So, the need for injectables certainly remains. And then you have the emergence of cell and gene therapies and other more targeted genetic focused therapies, many times requiring very precise local administration, whereas, just in terms of quantity of drug substance there, it would be very difficult to do systemic administration. Sometimes it would be impossible to actually reach the desired anatomical location.

And by virtue of that, you need some type of device to administer it in the right place, at the right time, in the right manner. And [there are] challenges. That has not always traditionally been done. There are certain cases that it's by typical intravenous administration. But then we're seeing more unique and targeted routes of administration. We're seeing direct central nervous system administration to various locations. And with those, pose new and different challenges that even the regulators are trying to figure out.

Throughout this conversation, there's an open invitation for any of you to echo or add or counter or supplement or redirect, but at any rate, you don't need to wait for me to follow and ask another question. But I will in this one case. Anybody want to echo or add?

Dorgan: Yeah, I can talk. I think there's, speaking to the at-home use, there's been a real drive towards taking traditionally IV-delivered therapies and trying to get them either into the sub-q [subcutaneous] space or bring them into the home environment or into a more user friendly. There's an access issue. We are a more globally dispersed population. Healthcare access is a big topic, not just in the U.S., but from a global perspective. So, creating solutions that have an access piece to them and delivery solutions from a therapeutic where, okay, I don't have to go to a center of excellence or I don't have to drive three hours to go to an infusion center to get by my chemotherapy every week or multiple times a week.

So, drug companies are looking at innovative ways to say, how can we work to either reformulate drugs to reduce some side effects or things to reduce having two, maybe three effects that you would have to stay under medical supervision to receive the drug. Or how do we reformulate the drug to make it at a smaller volume so we can put it in a delivery system that can be at-home use? Or do we put it in some kind of device that we can go through a specialty pharmacy or through an at-home care nurse that can provide infusion at home.

Walzer: I’d like to add to that is, also, the whole supply chain is becoming very critical to reach to the home use. It's no longer just a cooler with a temperature thermometer stuck to it to get it to the patient. The strategies and the challenges need to be really thought out as these drugs, large molecule, cell and gene therapy, are very temperature sensitive. It's all about the patient, making sure that the requirements of the product are met through the entire supply chain from manufacturing to the distribution center to the refrigerator at the house as it becomes more home use.

And a lot of technology is starting to center around digital, cloud-based temperature monitoring, traceability, predictive analysis, serialization using smart chips and real time analytics to ensure that you're maintaining product stability throughout the entire chain.

It’s easy to do a small clinical study to handle the temperature control when all eyes are on it. But when you start to scale up and you go commercial, if you haven't planned it out or thought it out and your design, your packaging testing, your temperature control, you're going to have some challenges early on.

So, design it early, design it often. Look for alternative suppliers. Have a device strategy, understand your cost. Packaging is usually the afterthought, but usually you have to — to do it right, you have to incorporate all that early on, especially as it relates to testing and impact. And/or have dual suppliers. You should also be thinking about customs, clearances, and the ever-critical last mile from the warehouse to the home is starting to be getting a lot of visibility now.

Okay. So, we've touched on it, but I'd like to hear a little deeper dive, if any of you want to take one on any of the therapeutic targets out there. What are we seeing in the landscape of therapeutic targets that's perhaps influencing the way delivery needs to be thought of these days or will need to be thought of in the future? What opportunities and challenges are there to expand the repertoire of what can be used and the landing sites for what kinds of therapeutic targets can really be treated more effectively if we change the way we deliver them?

Amaya-Hodges:

I'll take this to start. I think the newer modalities of therapies [are] driving a lot of this, certainly biologics in general. But I mentioned cell and gene therapies. So, the cellular therapies themselves, obviously that leads to more sensitive drug product. You have viral vectors and gene therapies. Those are also sensitive in their own difficulties.

Then even in the more traditional space or towards a more traditional space — nucleotides, mRNA, siRNA, even direct DNA therapies, they all have nuances in terms of delivery and sensitivities. Some require cold storage for the long run and have to be thawed, basically at time of use. Some have preparation steps, lyophilization, etc. So, these are all opportunities for devices to be used for preparation and administration.

And in my mind that's the biggest, It's not really about therapeutic area. It's about drug modality. And we're seeing an increase across the board of all these to treat therapies, especially. Again, a lot of this is borne out of the Human Genome Project and the advancements in genetics and the ability to target specific genes that we know are associated with disease.

Walzer: I think there's a major shift towards personalized and precision therapies. Customized, specific for you, almost a custom cocktail created for you. Eventually, it’s going to get to the home use customized for you.

Dorgan: Yeah. I think the other piece is the combination of therapies. So, combinatory therapies, so it’s not just, okay, we have this one therapeutic modality we're targeting. We're having two therapeutic modalities: We're going after this target and this target. So, people are doing double targets to address diseases, especially in the immunology space. So, the immunology space is just really blowing up right now. People trying to do multiple targets in the immunology space, especially in the biologics.

And so, can we create, whether it's proteins, peptides, different things that we can combine them, make dual target or dual antagonist drugs where we have multiple targets. Therefore, have the hypothesis that it may be more effective or may have additional suppression. And therefore having a have a more therapeutic, higher efficacy, more therapeutic effect.

However, some of those come with higher challenges with potentially having a greater immunogenicity effect or just higher reactive effects, especially in the biologic space. So that that can make some of the challenges there.

But I think the other area that people are targeting, there's a lot in the CNS space, trying to get past the blood-brain barrier. We’ve seen real advancement in nanoparticles and, again, in some of these very unique types of delivery systems, whether it's in these vectors or these plasmids, these unique ways to encapsulate all sorts of things: drug products, plasmids, again, you name it. But how do you get across that blood-brain barrier not just injecting into the brain, but putting it somewhere where it can get across the blood-brain barrier and it can stay across the blood brain barrier to treat some of these diseases that are in the brain and have been traditionally difficult to get to or in the spinal cord that can be really devastating and progressive. So, we've really seen targeting therapeutic areas in that area as well.

And that comes with its own unique challenges as well. There's a lot of sterility issues there and endotoxin limits there. And so, you go back and that goes back to manufacturing processes and just a higher level of concern when you're talking about the brain and that anatomy space that you need to have control over. And that just introduces a whole other level of controls that you need to ensure you're maintaining when you're producing those types of products.

Gotcha. I'm about to shift. It's probably a little bit of an artificial shift, but to shift the arena that we're imagining the folks in from the patient landscape to inside the biopharma organizations where people are working on developing therapies and treatments to target those patients. But before I do, does anybody want to add anything to or respond to anything that we've heard so far?

Bobo: Tom, I've got one maybe that can help us make the transition, If now's a good time. So, I think drawing back to some of the points that have been made so far. We see a lot of — it's an exciting time, right?  So, there's a lot of new therapies, a push to administer things that have historically been in an IV into home delivery.

So, what we see a lot of is, people doing this for the first time. It's exciting to move, say, from an IV to a device. It's shiny. There's lots of features on it. And people generally, that initial engagement can be an exciting time, right? Where we're moving into a home health care or we're trying to make our administration more usable in some capacity.

So, there's this immediate jump into selecting the first device you see and load it up with all the features. And I think — I'll steal a phrase from somebody on our team that says this all the time: It's a good opportunity to go slow to go fast.

And that's a good time, especially for companies that are getting into this for the first time to hit the pause button, really think about what are the needs of your user, your specific use case and what features or risks are you potentially trying to design around or [what] risks are you trying to mitigate against? Because these are things that become very meaningful, and the time to understand your core needs is early in that project, right?

Because it cuts both ways. We see a lot of teams that get late into development and realize they're missing key features, right, that now are very expensive to go back and try to redesign around. Or, on the flip side, you can have teams that select things that they think they need [but] they don't really need them. Those things end up failing during testing, during verification studies, and now you're going through lengthy redesign efforts, right, to address things that, if you went back to square one, a lot of teams would agree, well, maybe we didn't need this feature.

So, as we've seen a lot more of these molecules, new administration techniques, it's a good time for teams that are getting into that for the first time to just be aware and thoughtful as they merge into that device landscape because it is new, right? It's different than just IV administration.

What are some of the other key considerations that come to mind? And certainly, that technology selection and transition is obviously one of them.

Thorpe: I can maybe start the team off on that one. So, as we've been talking about this influx of companies just diving into more patient accessible combination products, there's a lot of pressure that we see of companies to try to get to market first. Or, truncated timelines, how quickly can we do it? And that's where the strategy is so important to what Bryan noted is, if you don't have the strategy of having that strategic vendor selection and doing it thoughtfully and taking your time, that will save you time in the long run.

And ensuring that you understand what you need to leverage from your vendor, ensuring you dive deeply into their technical files. What justifications are you going to need to make? A lot of the time will be saved by leveraging their documentation or their studies that they've done. Let's say they've already completed human factors, or they've performed certain testing that you don't need to repeat.

And then another area that we see that's lacking is also in their vendor agreements. What quality agreements do you have? What technical agreements do you have with these vendors? To get the information that you need so that you don't go through your whole development process and then in the very end, you realize, I'm getting an IR from the agency, and this device vendor won’t give me anything. It's not in our agreement to do so.

So, keeping those things in mind and strategizing early on before you dive into your development and doing that strategy piece first can really save a timeline.

Dorgan: Yeah, echoing on that, the strategy piece is key. And then not forgetting your regulatory strategy, engaging with the health authorities, whether it's the FDA, the EMA, or any of the other international regulatory authorities that you may be pursuing, whether from a clinical application or a commercial launch application early. People often forget that you put in a meeting request and then sometimes it's 30, 60, 90 days until you actually talk or get feedback. That's almost a quarter until you get feedback. I don't know many development processes that you ask a question, and you get a quarter to wait until you take action on.

I know Albana has been on many development programs, and I don't know any time where you've been able to say, hey, I have a question. I come back and say, I'll get your answer in a quarter.

So, planning that regulatory strategy, making sure you’re lining up when you want to engage with the health authorities and you understand that timing of the engagements can really ensure that you've taken advantage of those opportunities early and often, to get your questions answered at the right time, at the right cadence.

Don't be afraid of going to the health authorities for the questions, but plan out that timing in advance. And be strategic about the questions you're answering, so you make the most out of those engagements when you do have them.

Amaya-Hodges: The drive for being fast is always there. On the other hand, combination products are still a niche kind of segment of the overall market. It's vastly different than just developing an oral solid dose, than a vialed product for infusion. And it really requires that cross-collaboration between a whole lot of people with differing backgrounds and perspectives. And that has to come together to make a singular schedule to come to market.

In my experience, I've seen every permutation by this point: teams that are very disjointed, teams that don't have effective project management. But the end result of all that is delays from what is communicated or expected. Nobody wants that. Investors don't want it, but particularly the patients don't want it. These are either patients waiting, enrolled or enrolling in a clinical trial that could be helping to advance an important therapy.

Obviously, commercial marketing: it's a big deal because there are patients who might not be able to get their medication at all. Or not have it in a more convenient form. And so, in the end, it impacts them, going back to the patient landscape. So timing, getting the timing right upfront but then adapting as there's new information, new feedback, changes, etc. to something that's still reasonable versus trying to be on the bleeding edge and constantly running behind.

Thorpe: Organizational understanding of combination products. So often we deal with a lot of companies that are in a vial, they are pure pharma, never dove into combo products or devices. But having that knowledge internally so everyone knows what part they play, because it's so many different functions that have to come together and understand what their role is, what their pieces in that puzzle, is so important.

So having that internal training of, here is what combination product development means. Here are all the functions that have to come together. Here's what the combination product will look like. Here's what good looks like. That goes a long way. And that's really what delays folks the most because sometimes, we often see folks doing things in silos.

The RA team is doing their piece of the filing. The quality team is doing their piece of a few DHF [Design History File] documents, and no one's really cohesively working together. So that could really save a timeline as well.

In your continued work and your continued observations of the landscape as you look out over the next three, six, twelve months, what are you personally each most interested in keeping your eyes on and learning about and potentially reporting back when we get together again?

Dorgan: I'm really excited to see where the industry goes as far as looking at these unique, complex delivery systems, especially these combinate therapies. So, we talk about combination products in the sense of it's a drug and a device. But we're getting some more unique drug-drug combinations and a device. And that's starting to introduce a whole new host of interdependencies and some really interesting technical challenge from compatibility with container closure and stability challenges, and just technical challenges that are from an engineering perspective kind of fun to work through and challenging. It's not just the simple small molecule in a syringe anymore. Again, like I said, we're targeting different targets and trying to put them into a drug. That's introducing higher viscosity challenges, larger proteins, looking at more unique delivery systems.

So, seeing where that field goes and trying to solve some of those interesting engineering challenges in that drug space. That’s getting me excited.

Good. Look forward to hearing what you think in a few months. Anyone else want to point to the future and wax philosophically about what you're going to pay attention to.

Bobo: I have my eye on the prevalence of device platforms. It’s just a very hot topic right now and starting with the dream of, everyone wants a device platform. It's the silver bullet, it allows us to get to market quicker, plug and play. I think in reality, though, we find that it's not quite that simple. And oftentimes what we find is, you can develop your gold standard design inputs, for instance. But, if you're going to take on a platform, it is a much bigger organizational philosophical view that you have to shift your organization's mindset on.

I think it's something that usually, when we begin to interact with teams that are looking to go down this road, it's first making sure that as an organization they're aligned on what do they even mean by developing a platform. It's a term that gets thrown around a lot.

But what you what we find a lot of times, as you talk to different departments, they have different takeaways on what a platform is intended to achieve for them. And it's so common that we see teams invest a lot of time and energy into development of these things only for them to kind of fall apart because they are missing that sort of cohesive organizational alignment on why are we doing this? What's the intent of this?

And I think the second piece that I'll add that comes into this is I think the teams that do this well are also thinking about, if we're going to develop a platform to expedite our time to market, also thinking long term about how are we going to sustain this platform?

So, a future state when we have many multiple molecules leveraging from this or when we have new regulatory information that's coming in or guidances are updated, right? Thinking through, how are we going to update this platform? How are we going to push and pull that new information to and from it? I think it turns out to be, what can be seemingly simple technologies on the surface can become very difficult and challenging kind of systems engineering programs to drive and to get an organization aligned around.

So that's definitely an area that that we hear a lot about and talk a lot about with our clients. And I anticipate will continue into the future.

Yeah, thanks for sharing that one.

Walzer: Yeah. I would say for me, personally, it's digital health as it relates to digital platforms, whether it be wearable, mobile health apps, remote monitoring, personalized medicine, and how that technology is evolving really fast and making patients’ lives safer, more effective, and how that all gets integrated into the different ecosystems and a lot of challenges there.

Yes, sure.

Thorpe: I guess for me is the on-body delivery space. I worked on it in the past, and I'm excited to see what new on-body delivery systems will be coming out and actually commercialized. And then also the large volume delivery space. I think that's picking up. And that'll be really interesting to see how that evolves. So, I'll be keeping my eye on that.

Good.

Amaya-Hodges: And I continually follow, which is just the global evolution of regulations of combination products. The US continues to evolve. [Recently] there was a guidance, UDI [Unique Device Identifier Requirements] for combination products, that came out. So, even in probably the most mature market for combination product regulation, there's still updates ongoing.

And there's still really good discussion going on at industry conferences, whatnot. But globally, it's even more; Europe has changed a lot, continues to change. And then there are other markets that are coming up with their own schemes or deciding which route to follow or whether to deal with it at all. And, you know, it's very dynamic.

And of course, all companies probably come in and say, we want to focus on the US or U.S. and Europe, maybe Japan once in a while. But then they say, well, everywhere else. And then you run into, okay, well, what specific data do we need for wherever? Because these products can be regulated quite differently. And so, then again, we get to work through challenges trying to figure out where things stand today.

And yeah, I mean, eventually it's about how do we then get the therapies to the patients that need them wherever they are.

I want to thank all of you for joining me for this episode of In Combination. I very much look forward to having you share your perspectives again with us down the road. And to our audience, thanks for joining, and we'll see you next time.