Formulations, Devices, Regulations, and Patients: Two Takes On Drug Delivery Trends

In this unique episode of In Combination, series host Tom von Gunden, Chief Editor at Drug Delivery Leader, puts himself in combination with DDL Executive Editor Fran DeGrazio as the two share perspectives on drug delivery trends. Tom and Fran consider such topics as the regulatory landscape for delivery devices and combination products, formulation and delivery challenges for high dose biologics, and advanced support for in-home drug delivery and patient self-administration.

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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 your host for the series.

Today, we have organized a very unique and interesting version of an In Combination conversation. And that's because, in part, I'm one of the participants. So, today's In Combination combines two folks who work, at least in some parts of their day, in editorial capacities for Drug Delivery Leader. That's me as the chief editor, and that's Fran DeGrazio as executive editor. Fran and I are going to talk about trends and movements that we're seeing in the industry and are of interest to us, comment on them, and then point to the future toward the end.

So, before I tell you a little bit more about my background and where my perspective comes from, I want to introduce and welcome Fran to today's conversation. Welcome, Fran.

Fran DeGrazio, Executive Editor, Drug Delivery Leader:

Thanks, Tom. I’m very glad to be here, and I think this is a unique take on In Combination. So hopefully it will keep everyone's interest.

Well, good. I hope so as well. So, just to set the background a little bit, so you can you can get a feel for where my perspectives come from and where Fran’s do, I'll start by saying that, although I have followed the pharmaceutical industry for years – and, in a former capacity, I was chief editor on our Pharmaceutical Online site, which focuses mostly on small molecule manufacturing -- I'm only fairly recently a monitor and follower and commentator in the drug delivery space, specifically. Actually, only in the latter part of 2023 did I begin to set my sights on paying attention to the space. So that will probably inform and demonstrate some of where my thoughts and questions come from in today's conversation.

Fran, do you want to relay any background that you think might be relevant to demonstrate where your perspectives come from and what they're informed by?

Sure. My background, at least some of you out there know, includes almost 40 years at West Pharmaceutical Services, where I was heavily involved in packaging and delivery systems. And now I've been consulting these last few years since I retired from West as chief scientific officer. So, certainly my background is not only technical, but really a good understanding of regulatory and the market and challenges that people in the industry go through. So really looking forward to our conversation today.

Well, great. Thank you, Fran. And just so the audience can have a sense of the roadmap here, Fran, before we had hit the record button, you and I talked about three major topic areas for today: The first being the relationship between formulation and device,

the second being the regulatory landscape, and the third being the patient perspective. So, I just want to let folks know that we'll move in those three areas in that flow. And then toward the end, we will point to the future -- the near and far horizons -- and comment on what we see and are eager to hear about and study there.

So, let's start, Fran, thinking about the formulation and delivery alignment challenges. I'll just briefly comment on some of the key things that I hear all the time in my conversations with folks in the industry. And that is -- especially in the world of complex formulations and large molecule biologics – that there are obviously trends toward things like moving treatments from the hospital or the clinic into the home for self-administration where possible. Also, moving routes of administration from, for example, IVs to subcutaneous delivery, or from subcutaneous delivery or injections to oral administration where possible.

So one of the things that maybe I shouldn't have been surprised, but I think I was a little bit surprised about when I first started to network with folks in the drug delivery space, was a very common theme: In many organizations, the formulation side and the device side, so to speak, and even using words like side would suggest that they can often operate in functional silos. And perhaps more collaboration and interaction would be helpful.

So, I think I'll just start there: How do you see the typical way that formulation and delivery are developed and whether that's in tandem? And organizationally, how does that work or how should it work?

I know one of the blog articles that you did for Drug Delivery Leader focused on that topic. And, by the way, there's a little promotion here: Fran has a monthly column on Drug Delivery Leader called Frankly Fran. So that's what I'm referring to.

To me, that's where it all starts, right? And to your point, historically, there's a lot of functional silos in pharmaceutical companies. But certainly, those larger companies and those that have been around for a while now have recognized that this isn't something that can happen within one function, right?

When we're talking about bringing what ultimately is a combination product to market, there are multiple functions that need to be involved in that. And so, I think it really starts with getting the right organization together. And some of those key functions, certainly formulation development, packaging, your delivery systems, someone that understands how to bring all those pieces together -- those are all critically important during your development process.

And so, this whole idea of combination products is really breaking down the barriers amongst these functions if they want to be successful at this.

Yes. And I want to point folks to a previous episode in this In Combination series that ties directly to what we're speaking to. In that episode, I spoke to three functional area leads at GSK. And they talked about how they work together and collaborate in the early stages of the formulation and device selection alignment. I spoke with a formulation scientist there, as well as a couple of folks who are more closely aligned with the device selection side. One of those people, somewhat coincidentally, being named Dominick DeGrazio. I believe you know him, Fran.

Yes, I do!

What I learned from those folks is that, obviously, any kind of alignment that can happen should happen frequently, and it should happen early. One of the participants mentioned, for example -- especially with the idea of getting things more and more into in-home, self-administered scenarios -- that more and more clinical trials are occurring in in-home scenarios. And so, the earlier the better to get things ready even for the clinic, let alone for commercialization.

Well, that's a great point, Tom – the earlier the better that all these things come together because, ultimately, what you're looking to do is manage risk, right? And those risks can be technical. Certainly, there's a potential for compliance risks.

And so, the sooner that you engage all these groups together effectively, the better the opportunity to mitigate those risks. We hear a lot of trends now, certainly in the area of delivering biologics. We want to deliver higher concentrations and, therefore, there are higher viscosities, as an example. Those are things that, again, with all these people engaging together early in the process, they may be able to mitigate some of the challenges of that to then help to accelerate their program into development.

So, let's move into our second topic area, and that is the regulatory landscape for drug delivery and combination products. I'll start again by candidly offering what my initial and now current understanding of what's out there is like. So, one of the things that, again, maybe I shouldn't have been surprised about, but was -- and certainly I continue to be interested in, particularly in the combination products landscape -- is that there's still a great hunger for more clarity around things like, for example, what is a combination product?

What constitutes a combination product? How do you define one? How do you identify one?

And then things like, who's responsible for it across the range of the sponsor company, perhaps contract manufacturers, perhaps component or device suppliers? And then questions, for example, like which guidances, coming from where, actually apply? And then, of course, when you ask that question, what does that mean globally and does that differ?

So, I'll just position that in front of you to just say that I know there continues to be an eagerness for greater clarity. And here at Drug Delivery Leader, we keep working on helping to provide that. For example, you've joined me, Fran, for online live events on topics such as the QMSR, the EDDO, the URRA. And we'll continue to do more of those. So, I'll just pause there and see what your thoughts are in terms of those clarifications and, moving forward, questions and issues around regulatory.

Yes, regulatory, absolutely, is always a challenge. Because regulations continue to change and evolve. And that doesn't only happen in the U.S. marketplace, but globally. So, from that perspective, you really need talented people to keep an eye on what's going on out in the market. And I know that's one of the things that we try to do with DDL is to stay on top of some of those key pieces that may have an impact on things, such as combination products or medical devices.

So, absolutely we need to continue to focus on those challenges. There are differences, certainly, among each of the regional areas, but there are also commonalities. And there are also aspects in ways that, by leveraging ISO standards and ICH guidances and things of that nature, they can help to bring these global aspects a bit closer.

Just recently, as a matter of fact, I read about an International Pharmacopeia group that works together and got agreement on the elemental impurities, which is ICH Q3D. And with that harmonization, you're talking about the U.S., India, Europe, and Japan, and that they will then roll out regional guidance on all of this throughout 2025 and 2026.

But the real point being, they got global agreement as to how you should test for elemental impurities, and test methods and validations and all those kinds of things. So, although it takes a long time to develop -- and I think that team was working on that for close to ten years -- the reality is now you have it.

The next issue, though, is how agile are you as a company to quickly adopt these things that can actually build some efficiencies into your organization?

Gotcha, gotcha. Well, would you like to turn the page to our third and final topic chunk?

Sure. Well, I think it all starts with the patient. And so, I think that's one of the key areas that we wanted to talk a bit about. And when you're talking about a combination product -- a drug and biologic combination product -- it all starts with the end, right? That end user, and understanding the patient and the patient's needs. And then, of course, tying back upstream into what drug target product profile – TPP -- is going to get there for you. And certainly, the user needs for the device side. And how does all this come together? So, the patient aspects are extremely important. Tom, what have you been hearing?

Obviously, we have been monitoring the patient landscape and needs and so forth, and the patient centricity goals across the industry since the beginning of my time covering the drug delivery space.

But I think my keen interest really got triggered when you and I put together and hosted that live event on the topic of URRA -- Use Related Risk Analysis -- guidance. And we brought in a couple of human factors experts to join us to talk about that. And I think what I'm most keen on monitoring and following, based on the interest that was sparked there, are the continued attempts to have the delivery device, to make successful administration less reliant on patient age, skill set, that sort of thing.

So, the extent to which the combination of the IFU, the device design and reliability itself can ease the burden on patients having to think too much about how to actually administer these things, particularly in this movement towards more and more in-home use.

And I think the other piece to not forget is being able to leverage understanding from patient communities and things of that nature. There's a lot you can learn from patients who are living with many of these chronic diseases on an ongoing basis. And how can you take that information and really bring it back upstream to your scientists and engineers? So, yes, ultimately it all starts and ends with the patient.

Right. And I just want to point out to our audience, that in your “Frankly Fran” series and across some of the comments that you bring into our live events, you've certainly had a consistent set of references built out there for folks to look at around the patient perspective and things like patient safety and, as you mentioned just now, patient communities.

So, I appreciate your continued focus on not only thinking about that but also reminding our folks out there of what to focus on in that area. So, let's turn the page, or not really turn the page, but let's look toward the near horizon or the farther horizon.

Certainly, the nearer one is closer, but hopefully we can get to the farther one sooner. What are you most interested in that you want to continue to monitor and see developments in and pay attention to regarding the advances that we will commit to continuing to inform our audience about?

Well, certainly, I think, a key area -- and I know it's really broad -- but the topic of innovation in this space, whether it be with new therapies that are coming out, new ways of delivering these therapies and the challenges associated with that.

Even when we talk about that, another major trend is around sustainability. And the reality is, you're not going to be able to make these products more sustainable unless there's innovation applied, right? So, this is where some of the major trends meet, in my mind.

And then lastly, I think one of the other areas -- and I tried to allude to it in some of what I spoke about earlier -- is just efficiency, in general. People are looking to try to understand how we can be more efficient in development and approval processes. And so, things like utilizing platform devices and trying to figure out “How do we bridge across multiple drugs that are in a similar device?” How do you file and submit information so that it's easy for the regulators and the reviewers to understand? And so, I think those are all areas that we'll hear about a lot more in the future.

Yeah, yeah. And as I look out there, when I think about the urgency, about bringing things that we would hope aren't delayed until the farther horizon but actually come nearer to hand -- again, back to the patient population and patient perspectives that we talked about earlier -- I think about things like -- and these are things I'm learning more and more about, some I wasn’t even aware of -- for example, this is not one I wasn't aware of, but the idea of really bringing personalized medicine to people and personalized therapies, especially for people that have rare diseases, that have often been unmet, in terms of treatments. And so, the advances that can come and bring those closer to hand.

And then other things that I hadn't really thought about -- because fortunately, I don't suffer them myself. Things like patient populations where there is a challenge in not being able to receive certain drugs and therapies through certain routes of administration.

For example, I did an interview for a videocast series that I do called Sit and Deliver where I learned about dysphasia, which is difficulty and/or impossibility in swallowing, really. And in terms of taking medications orally, how do you address that for folks that perhaps the common way of delivering a medication that they need would be orally, but they can't really easily do that?

Or I did another interview for the Sit and Deliver videocast series and learned about gastroparesis: folks that cannot easily process things through their stomachs, food obviously, but also medications. And so, I think that's another portion of the patient population that I would love to see advances happen that bring relief to those folks, rather than on the farther horizon, on the nearer horizon.

And then I think, one last thing -- and I know we're planning to increase our coverage around this -- is combination therapies or combination medicines, particularly, combinations of drugs and biologics, especially where perhaps there are two mechanisms of action or multiple mechanisms of action that that need to happen in sequence. And how does that work? And so, I'm very interested in the technology and the science that will bring those things into more effectiveness, and particularly in targeting those folks with rare diseases. I'll just pause there and see if you have any thoughts on that, Fran.

Yes, I absolutely agree with you. Personalized medicine really has been a hot topic for me for many years. Because certainly it’s about the drug itself or the medicine itself, but it's a whole different concept or can be a whole different concept around the supply chain of how it gets distributed.

How does it get made? What is it packaged in? How does it get delivered? And so again, it all goes back to the innovation that I spoke about earlier. So, I think that's just one of many topics that hopefully we'll get a chance to discuss further, in the future.

And I just want to remind our audience of some of the ways that they can keep up to date on what we're working to keep you up to date on. And that is, for example, as I mentioned before, Fran publishes a monthly article called Frankly Fran. We actually push those out in a newsletter on the second Thursday of every month. So, if you haven't subscribed to that, I encourage you to do so. You'll also find the Frankly Fran articles on the Drug Delivery Leader website. And I often, actually always, promote them through my own LinkedIn posts. So, you'll have a way to find those.

As I mentioned, I do several videocast series. This is one of them, In Combination. I just mentioned one called Sit and Deliver. I also have two others. One is called Supplier Horizons, where I speak with suppliers to the industry about innovations, and mostly around what therapeutic areas and patient needs require or could benefit from innovation.

And then I also have a series called The Combination Products Handbook: The Series. And that is a series that goes chapter-by-chapter through a book edited and coauthored by Susan Neadle. Also, Fran is a coauthor in one of the chapters in that book, and there's an episode in the series that features Fran.

So those are videocast series to keep up with. And then also, as I mentioned, we do a series of what we call Drug Delivery Leader Live events. And those are live online events with panels and audience Q&A opportunities. So those are among the many ways that you'll have opportunities to hear from Fran, and me, and others on the topics that we discussed today.

So, thank you, Fran, for joining me. And thank you to our audience for joining me for another episode of In Combination. And we'll see you next time.