Leveraging Platform Technologies In Drug Delivery With Suttons Creek

In this episode of In Combination, Paul Chao and Carolyn Dorgan from combination product and delivery device consultancy Suttons Creek join host Tom von Gunden to discuss strategic considerations and best practices for employing technology platforms in device development for injection-based delivery. The conversation illuminates aspects such as the design space across product assets in development, component options within a platform offering, and regulatory pathways for platform-based submissions.

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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 episode. Today, I have the pleasure of being joined by two folks for the conversation who are from Suttons Creek, a drug delivery and combination products consultancy.

And from Suttons Creek, first off is Paul Chao, who is SVP there.

Welcome, Paul.

Paul Chao, SVP and Division Head, Suttons Creek

Thank you for having me.

And back again for another Drug Delivery Leader asset, is a familiar face for our audience, Carolyn Dorgan, who is VP of Solutions Engineering at Suttons Creek.

Welcome back, Carolyn.

Carolyn Dorgan, VP Solutions Engineering, Suttons Creek

Thank you. Glad to be back.

Well, it's my pleasure to have you both here.

So, we have determined that we're going to talk about platform technologies, and specifically how folk in biopharma organizations who are involved in some way with strategy decisions and the work of developing products that will be delivered might want to be — might already be — thinking about or might want to consider platform technologies.

And I just want to make a quick clarification before we turn to that: When we talk about platforms here, we're not referring to biologics-based platforms, those nanomedicine kinds of platforms like vectors and nanoparticles and things of that nature. We're talking specifically about platform devices or platform delivery systems. And probably most of our examples in that arena will be things like autoinjectors and device-oriented combination products.

So, with that framing as background, it might be helpful to start by talking a little bit about what the concept of platform might mean, or means, to people. There can be a range of interpretations of what people mean when they say “platform.”

So, let's start with the concept and definitions. If you can help start on that, Carolyn, I'll turn to you to do that.

Dorgan: Thank you, Tom.

One of the hot topics and terms that has been thrown around the industry for now a couple years is platform. It's a love/hate relationship among many industries with the term platform. A lot of the large pharma companies out there now are working on platform initiatives and trying to implement them within their organizations.

But what does platform actually mean? And what do people mean when they say “platform”? Oftentimes, different people within the same organization may even have different interpretations of what platform means. And in our work here, we definitely assist with platform initiatives. And with that, there are different interpretations.

At its base level, a platform really is [this]: If you're taking a delivery system like a prefilled syringe or an autoinjector and you want to be able to create a set of data, a set of information, or a dossier that you can leverage across different assets. So, you may have one asset within your organization that's using an autoinjector, and you have three more in the pipeline that you want to use autoinjectors. So, you want to really establish that foundation so that the work you're doing on your subsequent asset Is less de novo information each time.

Now, the ideal scenario of a platform, what many C-suite executives think of as a platform [when they] say, hey, I'm going to develop an autoinjector once for one asset and I'm never going to have to do anything else again.

But the reality is that, when we talk about a platform, we're really just talking about a piece of technology. When we put that in combination with an asset, making it a combination product, then we're actually talking about, okay, the platform piece is a part of it.

So, when you have a new asset, there'll be a kind of delta there of anywhere from 50% to 70%,  maybe more, maybe less, that's leveraged between assets. And so. I think it's really important to understand and come into the conversation with the expectation that a platform approach does save you time, it does create efficiencies, but it's not the end of the road, it's not the end of the journey. Every asset will have its own unique challenges along the way.

Yeah, so it sounds like what you're saying, Carolyn, when you talk about the percentage of the way, along the way, that someone might be in developing a product leveraging a platform, is that we're clearly not talking about something in most cases, or perhaps in any case, that someone could say is literally just “off the shelf” and doesn't require any kind of adaptation. Is that a fair way to put it?

Dorgan: That's a fair way to put it. And I think it's… terms can get confusing because many of the different technology providers will call their systems platforms, but they may have different SKUs, different customizations. It may be something just as simple as different fill volumes or a different one of four springs that they have in their autoinjector that you're selecting from.

But you, as a pharmaceutical company, are giving those design decisions to the platform provider to create that custom device, that custom delivery system for you. There may be several changes between assets; there may just be one minor change between assets.

But that's what we really talk about as platforming when we talk about the spectrum and how much platforming gets you between assets.

Thanks for the foundational take there, Carolyn.

And before we move on to another segment, which will be an obvious transition, but Paul, I wanted to see if you had anything you wanted to add to or echo in terms of what we're hearing from Carolyn.

Chao: Not too much more to add other than just emphasizing the importance of level setting the understanding of the definition of platform. And Carolyn pointed it out already. There are different ways to interpret the terminology. So, just making sure internally you're all on the same page on what that means. And then you can build the necessary plans to execute to that strategy and approach.

Alright, great. Paul, now that we've got your voice warmed up a bit, I'm going to turn to you to offer the opening commentary on our next segment. What I'd like to start to dive deeper into now would be some of the technical considerations — science and technology considerations — that might come to the fore when folks start to think about whether or not a platform tech approach is suitable for the product development that's either planned or underway at their organization.

Chao: Yes, thank you, happy to kick this off. So, I would say that, ultimately, platforming is really just putting the plans and investments in place up front in order to save time and money later on. And I know Carolyn touched on that already. But you can do this by maximizing the amount of things you can leverage, down the line, right? A lot of it is related to what can you leverage later on so you can save on time and cost?

So, for example, you can start considering the components for your product presentation and see if you can standardize them for your pipeline. Examples can be using the same primary container or stopper or safety system or autoinjector. You can then leverage the data down the line, such as, say, DV [data variability] data that you put together, [for example] needle shield removal force. That's probably something you can leverage down the line. That's not really expected to change depending on the asset. Or safety activation force or safety override force.

So, there are certain functional tests that can be leveraged down the line. It’s good to think through that if you're able to keep these components consistent. Then that's something that you can leverage for assets later down the line.

Another thing I'll say is that, by keeping consistent with the components, this can also help your supply chain. So, existing fill-finish, final assembly, and packaging lines can be leveraged, assuming, of course, that there's capacity. But at the very least, the technical risks for these operations are significantly reduced if you're able to be consistent with these components.

Anything to say about the patient side? There's such a trend toward enabling self-administration, in-home administration. Anything when it comes to usability or human factors that come to mind maybe differently when we're talking platforms versus custom, specific kinds of delivery system development.

Chao: I would say, if you're thinking of a platform framework and mindset as it relates to usability, you just have to be a little careful, right? You can certainly do it, but it would mean probably doing a worst case of your user population and/or adding more user populations to accommodate your potential pipeline molecules down the line.

And so, to me, that would mean maybe longer recruitment time for said user populations or longer recruitment time for getting more user populations. So, definitely something that you need to be mindful of if you're planning to approach platforming from a usability and human factors standpoint. There are some advantages, but it could be some up-front work and time ahead of it.

Dorgan: I think that brings up an important point in the technical considerations: understanding the design space and the importance of that. When looking at your asset portfolio, it's not just the design space of the delivery system, but it's the design space of your drugs, your molecules, your biologics, whatever you're developing in your pipeline.

Where is that design space? Where are your viscosity ranges? Where are your delivery volume ranges?

Where are your patient ranges when we talk about human factors? Are we going into pediatrics? Are we talking about individuals with limited mobility? Are we talking about injection-naive patients or patients who are used to injecting themselves with a variety of different devices? Are we looking at hereditary conditions where you may have family members that may be taking different drugs, different doses of drugs, have different autoinjectors within their own household that you don't want to get mixed up?

So, there's a lot more to consider from that design space perspective than what people traditionally will consider in the design space. And doing that mapping exercise of your design space up front. And then doing it often as part of your portfolio planning on an annual or semi-annual basis can really help you in understanding where those efficiencies may be, or where those deltas may exist that you do have to have supplemental data.

In developing a platform approach, you often have to do a bit more than the bare minimum up front from a technical testing perspective, but it does save you time in the long run. So that's really kind of the trade-off that companies have to make when they're thinking about platforming and how to execute that.

Great, thanks. You mentioned a couple things in there that I think will be good transitions to our next segment, which is going to be about regulatory. And, Carolyn, I'm of course going to lean on you to kick that off, especially given your experience as former FDA.

You mentioned things like clinical data and testing. So, among the regulatory considerations that come to my mind — because folks in our audience I hear wondering things when it comes to platforms like, for example, if I'm leveraging a platform and I'm on a second or third or subsequent product, how much of my previous testing, if any, can I rely on for regulatory submissions? Folks are always interested in, are there any particular guidances at FDA or other jurisdictions that might help with the thinking about how to prepare for a platform product submission. Maybe even foundationally from your experience there or later, what's even the FDA view on platforms as an appropriate approach?

Dorgan: Well, there's no shortage of regulatory topics to dive into when we talk about platforming. You know, when we look at it from the FDA side, platform kind of becomes the taboo word in that, when the FDA is reviewing products, they're really looking at: What's this asset? What's this system? And how is it safe and effective for the population? They're not incentivized to say, hey, where can I create efficiencies across different assets?

Yes, theoretically, you could reduce review time or review burden, but the mandate here really is public safety. And so, that's looking at each individual asset uniquely in its data set as a complete data set.

But where platforming can be effective in a regulatory strategy is really being able to demonstrate that design space and that complete data set — understanding what's worst case, being able to articulate that.

There's a conflicting belief out there that's like, oh, well, everybody's used this prefilled syringe before. It's being used in one hundred different products that are out on the market. Why do I need to retest this? Well, maybe you don't need to retest everything, maybe you do. How is your product or molecule, your protein — how is that different from what's already on the market? And do you have access to that data?

That's one area people run into: hey, other companies use this. You don't necessarily have access or right of reference to that data. And so, the way the review paradigms work these days is you have to have the right of reference to it.

And that's what brings in the more interesting guidances that are out there. I know the EMA put out guidance on clinical bridging for mAbs, or monoclonal antibodies, as a potential pathway to say, where can we waive PK [pharmacokinetic] bridging studies?

One of the big initiatives is saying, okay, we're going from a vial to a PFS [prefilled syringe], or a PFS to an autoinjector. Why are we doing PK studies when really the primary container, if we're talking PFS, the autoinjector oftentimes doesn't change. The needle length is not changing. The area of delivery is not changing. Why are we reassessing changes, from a PK perspective?

The proposal that's out there from the EU is to say, okay, we potentially can look and say there are some similarities if I have the right of reference, if I meet certain conditions that would allow me to waive the need for an additional PK clinical bridging study.

The U.S. doesn't have a similar guidance, but there are similar conversations happening between companies and the FDA on saying, okay, where do I have that similarity? I'm using the same primary container closure, the same prefilled syringe I used for this other asset. I have the right of reference to that data, the differences between my two monoclonal antibodies are not significant or fall within the same design space. I can be assured that the delivery mechanics are not going to impact PK and, therefore, receive a PK waiver.

So, this is a really new area in the last six to nine months-ish that's been emerging, where we're able to leverage that platform approach in an effort to reduce clinical testing within delivery systems. Again, it's not widespread, and I caution people that it's more the exception right now than the rule, but there are studies looking into how we can use leverage to reduce that clinical burden.

Gotcha. Well, thus far, we've talked about some of the foundational concepts and definitions. We've outlined some of the key technical considerations and regulatory considerations. I think what we're really doing is teeing up a conversation about, how do people decide whether or not a platform approach is appropriate or beneficial for what they're planning to do?

So, Paul, I'm going to turn to you to start this one off. Let's talk about, maybe just frame it up very simply: As people are considering platform approaches, what would be some of the key considerations that might inform decisions like “yes or no?” or “why or why not?”

And I'm imagining that, in our audience, we would have folks who work in organizations where platform system adoption might come deeper into a product development cycle, where perhaps the formulation has been worked on, and now they're looking for the appropriate device to select. And maybe that's where they begin to think about a platform.

Or, maybe on a very opposite example, there might be folks out there who are in an organization who have made a high-level business strategy decision that we are going to be a platform development company, and we're going to continue to layer our additional product assets onto platforms.  

That's where I started thinking about it. Paul, I'll turn to you to see where your head is around it, and then we'll see what both of you have to say. But, Paul, go ahead.

Chao: I'll just say it depends on the situation, right? On the situation of the company and the urgent need. From my experience, oftentimes there is urgency in getting through the device development activities in order to get [a] combination product out to clinic or to the market. And so that might dictate whether you want to take into account the long-term approach of platforming. I think that's a critical part.

I would say, though, that it's good to at least reflect on the platforming approach, especially as it relates to deciding on the components for your combination product. Reflect on, at least, okay, do we think that a lot of our assets down the line are going to be in an autoinjector because of the needs of the user. If you can help [with] it, the volume and the viscosity range, which Carolyn touched on earlier.

But at the end of the day, it's all about the business need, and maybe even the patient need. Again, going back to the level of urgency, I'll say the other part of it is the cost associated with doing a platform. And when I say cost, it's not just the financial part of it, but also the time. Again, going back to urgency. And Carolyn touched on it a little bit earlier, where up front, you need to do a lot of planning. And with that planning comes the execution of that platform mindset. It could be building the worst-case data set  in order to achieve that way of leveraging down the line.

So, I think for those reasons, if you have one or two major assets that you're focusing on over the next couple of years, I really don't think you need to spend too much time on building a platform framework. But if you envision many more assets coming down the line, maybe four or five that can fit within that platform framework, then you get a lot of upside by investing up front on a platform approach.

So, it's not a straightforward answer, but those are just some considerations, I would say.

Yes, thanks.

Carolyn, do you want to add anything to that — echo or add?

Dorgan: Yes, certainly. Mentioning what Paul said, it does take time and money and investment up front. So, a lot of the organizations we see doing platforms are coming in and creating that platform dossier, that platform library, if you want to call it, of all the technical documentation after their second or third asset has made it to commercial.

And so then being able to streamline it in parallel, although there's complexities with managing lifecycle management and trying to create a platform design development file at the same time. But it's really at that transition point where you're moving from 2 or 3 assets to maybe 4 or 5 or 10 or 12 down the pipeline, where the business case becomes apparent to the decision makers within the organization. It's often not at that first asset.

We do see a lot of quote-unquote, “remediation into a platform” approaches, once you have those two or three assets, to be able to align those, make sure those documents are streamlined. And then you can take that and say, okay, what can I make consistent between assets? What's that delta that's going to be there? What can I pull from? And then place into each asset’s dossier. Once you have those  first two or three, they're really done in an independent fashion.

I like to end conversations like this for our audience with what people typically call “takeaways” or “words to the wise.” We didn't really talk this through when we got together to prep for this, so I hope I'm not putting either of you on the spot. I'm pretty sure I won't be. But if you could distill the conversation into any, maybe words to the wise would be a good way to put it, either cautionary — here are things to avoid, pitfalls to avoid — or hopeful and inspiring — here's how to best leverage the opportunity.

If you were going to point to maybe a decision point or a first step or some place that folks could look around in their organizations to say, we're either ready or we're not. Or to get ready, we might need to start here or look here. Where might you point people as good places to determine whether they're on the right path to making the decision to move forward with platforms or not. And then if they make the decision to do so, how to do so?

Chao:  I would piggyback off of what I mentioned before about what you need to reflect on up front and the urgency. I would say, probably start with thinking of the patient in mind. And when I say “urgency,” it’s less about… I know there's this business urgency … but it's really all about getting the proper products out into the market for the target patient population. And so, have that dictate the business processes internally to how quickly and efficiently you can get these products out into the market. I think that's a good lead, right?

But as a business, it's really important for us to reflect on, alright, what are the right business processes and frameworks and organizational structures that we could put in place in order to achieve that mindset. And platforming, to me, is definitely something that's worth a conversation with the key stakeholder and take at least an informed decision on in that regard.

 Gotcha. Carolyn?

Dorgan: And I'll start out with a word to the wise: Don’t rest your laurels on the fact that it's a quote-unquote “platform technology” from your CDMO and your regulatory submissions as a reason to do lesser testing or reduce. It's really about creating that scientific justification.

So, even when you are doing platforms, you're leveraging. So, understanding — I know I sound like a broken record — but understanding what is the same and understanding what the delta is and effectively communicating that is really important. Otherwise, you can create delays, you can get asked to do testing that may be redundant, just because you didn't articulate the reason why your testing on a different asset could be leveraged for this new asset.

So, really understanding that design space, being able to communicate it effectively about your decisions, why you did what you did, can really make platforming more effective, especially when you go into regulatory conversations where the word platform is not as warmly received. And that's not just in the EU, or in the U.S. In the EU, you are working with different notified bodies. Different notified bodies are going to have different interpretations of platform. So, getting that story consistent, referring back to the scientific data and the justification: that's really where we get products across the finish line and get them to patients quickly and effectively.

I didn't think that I was going to be fibbing when I said I think we're moving into our last question, which is about takeaways and words to the wise. But, in listening to both of you, I realize now I usually end all of my videocast episodes and almost every series I do with a look out over the patient landscape. And, Carolyn, you just referenced patients. So, I'm not going to let either of you off the call just yet. Let's extend that a bit.

Let's assume that the right folks choose — the people who should, the organizations that should probably choose — to develop platform core competencies and leverage it appropriately to scale and speed-to-market, as you were referring to, Paul.

If that work gets done by the right folks and makes the right kind of imprint and impact on the movement of products to market, what might the larger-scale permeation of platform-developed and delivered products mean for patient healthcare?  From clinics and clinicians to the patient receiving of therapies, whether that's done in a clinic or done at home or wherever: Do you see places where you could say, we can see the real patient benefit of the fact that these things are now, in some cases, being developed on platforms?

Dorgan: So, I think there's two sides to the story. There are always two sides to every story. Once you create that platform — you create that data set of information — your development times really reduce. And then you're able to bring new assets to the market, make lifecycle improvements, move from that vial to a more patient-friendly experience in that prefilled syringe or autoinjector, and get that out to patients faster.

And getting therapies to patients in ways that they will reliably take them is important. I don't want to undercut the patient experience, by any means, because if you don't like taking the drug, you're not going to take it. And what's the point of getting the therapies out there at that point.

But the flip side of that is when we do have platforms, we create market concentration. So, if there is an issue with one platform through all your assets. So, it's a cautionary tale to make sure that you're understanding that and working very closely with your CDMOs or your CMOs, and those technology partners who are developing those platforms to understand, okay, when they are making changes, when there are complaints coming into the field, how are we addressing them? And how are we addressing them across the spectrum of the different assets that may be using that platform?

Gotcha.

Paul, I saw you listening and maybe even taking notes, and I could see a little bit of maybe even a furrowed brow of thought. So, I'm guessing you're going to emerge with something to add, so what is that?

Chao: I'm thinking through, alright, benefits to the patient. It made me think, okay, by using these platforms more and more, you would presumably assume that we would de-risk the use of that platform, both from a technical standpoint — it would presumably iron out a lot of the technical risks there — and then also from a usability standpoint.

Let's just say a two-step autoinjector or something like that. Patients for that given therapeutic area become more and more familiar with the use of that platform. So, I think, in my head, maybe there will be less issues in the field, less use errors, potentially.

On the flip side, I'm thinking to myself, well, what could be the trade-offs of the growth of platforms? And I thought to myself, maybe supply? Maybe from a supply chain standpoint? Could you start to have more constraints from a supply perspective? But obviously, that can be fixed with adding new lines — production lines, assembly lines, and things of that nature.

So, definitely, I could see the patient benefits. I could see some trade-offs, but all, in my opinion, can be addressed.

Gotcha. Well, any final parting words that either of you just suddenly have a burning desire to leave for our audience before we close?

Dorgan: I don't really have anything, but I think this has been a good conversation, and probably one that's going to continue to evolve as the technology evolves over the coming years/ So it will be good to look back on this, maybe in two years, and see where we're at in the industry.

Sure. Well, perhaps that sets us up for a revisit down the road. But certainly, for today's conversation, I want to thank both of you, Carolyn and Paul, for joining me to share your thoughts and perspectives. And I also want to thank our audience at Drug Delivery Leader for joining us for this episode of In Combination. And we'll see you next time.