Going Deep On Delivery With The Subcutaneous Consortium

In this episode of In Combination, officers from industry association The Subcutaneous Drug Development and Delivery Consortium join host Tom von Gunden to introduce the structure and work of the group. The discussion of sub-team activities and outputs illuminates key challenges and innovation opportunities around bioavailability, immunogenicity, high dose formulations, sustainability, clinical development, regulatory strategy, and patient preference. 

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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 I am joined by officers from the Subcutaneous Drug Development and Delivery Consortium, and we'll be hearing from them about the work of the group. But before we do, I want to welcome each of the officers who are joining for today and have each of them introduce themselves in terms of their role within the consortium and what they do in their day jobs.

And I'll start with you, Donna.

Donna French, President and Officer, Subcutaneous Consortium:

Thanks, Tom. I am Donna French, and I'm president and officer of the consortium. I am also vice president at AstraZeneca of the dosage form design and development organization. And this group oversees the development of drug products and devices for the biologics portfolio.

Excellent. Welcome, Donna.

Sachin …

Sachin Mittal, Vice President and Officer, Subcutaneous Consortium:

Hello everyone. I'm Sachin Methel. I'm the vice president, officer, and also the Bioavailability sub-team lead for the Subcutaneous Drug Development and Delivery Consortium. In my day job, I'm an executive director at Merck in the sterile product development team developing vaccine drug products.

Welcome, Sachin.

Monica …

Monica Adams, Marketing Lead and Officer, Subcutaneous Consortium:

Hello everyone. My name is Monica Adams. I'm the marketing lead and officer and the Sustainability sub-team co-lead for the Subcutaneous Consortium. And in my day job, I work at GSK where I lead the packaging device and design solutions group.

Welcome, Monica.

David …

David Kang, Treasurer, Subcutaneous Consortium:

Yes, thanks, Tom. Hi, my name is David Kang. I am the consortium treasurer and officer. And in my day job, I'm the director of drug delivery research and Innovation at Halozyme Therapeutics.

Great, Well, welcome all.

So, Donna, could you give us a little bit of an overview of the landscape out there of trends and opportunities that make the work of subcutaneous delivery particularly pertinent and relevant and useful in today's landscape?

French: Yes, sure. Well, subcutaneous drug delivery: it's been a common mode of administration in many different therapeutic areas for a long time, particularly in chronic diseases — metabolic, respiratory, autoimmune. But that being said, there are many aspects of subcutaneous drug administration that are not well understood. And the goal of the consortium is really to advance our knowledge and close gaps that can help us facilitate drug development in this way.

And I should also add that many of the therapeutic areas that have had intravenous drugs traditionally — and I'm thinking particularly of oncology, but there are others — we're seeing this transition to subcutaneous. So, I think all of this has really driven our interest in having a better understanding of this space and really drive progress for all of our subcutaneous delivery consortium members.

Great. Well, thanks for the opening look at the landscape.

All right, so as we continue to look out over the landscape for a moment, what are some of the key challenges out there for folks working in the area of subcutaneous delivery?

Adams: I think there's really been a shift towards sub-Q delivery. As Donna mentioned, we're seeing this in new therapeutic areas. We're seeing scientific challenges, regulatory challenges, challenges in the commercial landscape.

Mittal: And if I were to briefly expand on what Monica said: at a high level, there are challenges that are associated with the delivery of high doses and high volumes of these medications that need to be delivered subcutaneously. So, there is unpredictability in the bioavailability of these medications, the immunogenicity, and clarity around regulatory expectations with regards to clinical bridging strategies are wanting. And there is variability in patient adherence and preference for these subcutaneous products, all of which challenge the development, commercialization, and ultimately the adoption of these subcutaneous products. So, overall, it presents a huge opportunity for us across the industry to make a difference.

Great. Well, that overview of opportunities and challenges will be very helpful as we learn more about the work of the group.

Donna, I'm going to turn it to you to give us an overview of the organization itself: the membership, the structure, how it organizes its work, and so forth.

French: Sure, Tom. So, the consortium has over 20 companies. They are mostly large pharmaceutical companies, but increasingly, we are having participation from drug delivery device companies.

We have a governing board that consists of the tier one members, and this board sets the overall strategic direction of the consortium. They identify and prioritize the key topic areas and agree on some sub-teams that will be formed to address each of these areas. So, at this time, we have six sub-teams that have been created to address some of these challenges that the consortium has identified at a much deeper level.

And each year, the governing board members have a face-to-face. We review what our challenges or problem statements are for each of these key topic areas. We ensure that we are still on target with those problem statements or maybe they need to be updated. We share what has been achieved and then discuss what we'd like to focus on and what our goals will be for the following year.

And at some point, we also, of course, sometimes have to prioritize these to ensure that they're doable and that they fit within budget. But by the end of each year, we usually have a pretty solid view of what we'll be doing in the following years. And then we meet regularly for progress updates, strategic topics, and more.

Great. Thanks for the overview of the structure and the work.

Yes, so let's hear more about the sub-teams, what they're focused on, and what the work looks like. Let's start with you, Sachin.

Mittal: Yes, thanks Tom. So, as Donna pointed out, we have six sub-teams. So, I'll start sharing a little bit more about the Bioavailability and the Immunogenicity sub-teams. So, as we know, the subcutaneous bioavailability of biologics is unpredictable and highly variable. So, we have reported bioavailability somewhere from 40% all the way to 90%. And the tools or the models in vitro, in vivo are preclinical, and the translation from preclinical to clinical is missing. Hence, what the sub-team is focusing on is trying to create these models such that we improve our understanding and predictability of subcutaneous bioavailability at the consortium.

And if you look from a similar lens to the Immunogenicity sub-team: [Regarding] the immunogenicity for subcutaneous products, there's a lack of patient-derived, real-life clinical data to understand the clinical relevance of immunogenicity. And so, what the team is trying to understand is, given that there are no harmonized industry-wide accepted models in vivo or preclinical for immunogenicity, how can we enhance that understanding? And so, currently the Immunogenicity sub-team is focused on developing an industry-wide accepted model for immunogenicity testing on various proteins.

Gotcha. Thank you.

David, would you like to tell us about a couple more of the sub-teams?

Kang: Yes. The third sub-team is CDRS, which is the Clinical Development and Regulatory Strategy team. As we look at how subcutaneous products are developed and improved, there's still a lack of cross-industry position on the most appropriate clinical development pathways for subcutaneous products. And so, hence, what the team is addressing is the strategy in clinical design and execution, as well as to form a basis for health authority interactions on this particular topic.

Another sub-team is the High Dose High Volume team. This sub-team is quite active, and they were formed as a cross-industry effort to address a number of gaps regarding understanding and implementation of a roadmap or best practices in something like CMC development for high dose, high volume products. This includes both in the formulation and device space as well as other projects, such as to evaluate and define opportunities in harmonization standards.

Thank you, David.

And if my count is correct, there should be two remaining sub-teams to hear about. Monica, would you like to tell us about those?

Adams: Sure, you got it. There's two left. So, the last two are the Sustainability sub-team and the User Preference and User Experience sub-team. The Sustainability team was formed out of a recognition that there really isn't a meaningful collaboration, guidance, and integration of the sustainability concepts across the full value stream for sub-Q products. So, what this ultimately means is that implementation is limited, and solutions are often developed at the local or company level so that we're not achieving the impact that we could. This sub-team has a number of streams which are currently evaluating many areas, from benchmarking all the way through to potential solutions.

The other sub-team, last but not least, is the User Preference and User Experience team. And this team is really focused on understanding the key perceptions and trade-offs, which will ultimately inform subcutaneous product design and help better direct the developers of sub-Q products. And I would also say in this space, this is an area where a lot of companies have their internal knowledge, but we don't have a wealth of publicly available information. And this team is really focusing on doing that.

All right. Well, thanks for that coverage of the work of the sub-teams. So, as we look forward to the work of the consortium and those teams, what are some of the key activities and outputs that should be expected on the horizon?

Adams: I'll take that. It varies each year. So, each year our sub-teams develop tactics and align those with the governing board for the upcoming year. But essentially at the end of that, what you will see is the sub-teams are typically highly involved in presentations and key industry conferences. You will even see us putting together workshops. I think David has a lot of experience in that space.

Kang: Yes, thanks Monica. Yes, we've organized and presented workshops, for example, at CRS this year. The sub-teams have also presented at various PDA meetings. And in addition to that, we do publish white papers as well as peer-reviewed papers on our stance and provide guidance to the greater community based on subcutaneous high-volume delivery as well.

Mittal: So, in addition to what Monica and Dave just mentioned around conferences and publications, one of the things we also focus on are research outputs. And these can include things like market research, new models that we have developed and sharing those, and other tools that would be of interest to the community.

So, within each sub-team there would be numerous ongoing tactics, as Monica alluded to. And these are led by the sub-team leads or subject matter experts, which are inclusive but not limited to position papers, the search on predictive models, development of manuscripts and reviews. And these are intended to address or provide answers to key challenges defined in the sub-teams’ problem statements.

As an example, the Bioavailability sub-team collaborated with a partner, an external partner, to develop an in vitro as well as an in silico model that helps better predict bioavailability. And we are in the process of publishing that original research output.

French: Building on what Sachin just mentioned, it’s important to note we're making a concerted effort to increase our engagement and partnerships with both academia and various technology companies so that we can produce more consortium-sponsored research. And even in our last face-to-face, we identified areas where we could fund research or even maybe clinical research together. And this helps us drive our progress further as a group than I think we could as individual companies alone.

Well, great.

Well, that sounds like a tremendous range of activities and a lot of promising outputs to look forward to. So, if folks who have been listening today or watching today are interested in learning more or getting involved, where should they go to do so?

French: If people are interested in participating and representing their company, they can go to the Subcutaneous Drug Development and Delivery Consortium website. There's a tab there for membership and also a link where you can fill out the information and send that email, and someone will get back to them with more details.

Adams: We're also on LinkedIn. So, if you just visit our site and click for notifications, you'll be able to follow our feed there as well.

Well, perfect. Well, I want to thank all of you for joining me today to give an overview to the Drug Delivery Leader audience about the work of the Subcutaneous Drug Development and Delivery Consortium. And to our audience, I want to say thanks for joining for another episode of In Combination. And we'll see you next time.