Welcome to Farmer Talk Radio. This podcast is focused on biomateial implants to reduce patient burden and improve adherence from the twenty twenty four pod Partnership Opportunities and Drug Delivery Conference. For more information on the pod conference, editorials, podcasts, or webcasts, please visit Drug dash Delivery dot org. Thank you and enjoy the podcast.
Our topic today is biomaterial implants for reducing patient burden and improving adherence. I'm joined by four fellow colleagues and the drug delivery and the device field and let's get started.
So there was.
A similar session earlier on a similar topic, but I think we'll have a different perspective perhaps, But before we start, maybe we'd just give a general introduction to what we mean by biomaterials and implants. So there's a biomaterial in this setting is basically any material that's coming in contact body.
Of course, for a therapeutic application, we have special requirements biocompatibility, maybe bioorotability, but an implant in the general sense could be any parental depot that's giving a long sustained release of an API. But we also have sort of a classical definition of an implant. I'd like to sort of ask the panel premier perspective, what do you think of when you think of an implant versus a other type of long acting injectable.
So I'm Jamie Sean with Pfizer, I head the Global Biopharmaceutics Group for introduction. Yeah, so I think I told the group at one time that from my classical perspective, something which can be injected is a depot injection or a long long acting injection, while something which actually has to be inserted or could be you are too implant, it is an implant. However, that definition is getting blurred, and I think the USB and the regularty Agency is
kind of don't differentiate it that way. However, there is an impact in terms of how we define implant as to how it is going to be designed and developed, and we can.
Talk about that later.
The other thoughts.
Yeah, I think classically we start with that to that point, jam In, you know, an injectable with a fixed geometry is something that would be defined as an implant. But if you expand it and taking into consideration the USB definition is it's injected, it's probably localized at a certain site, and from that site, it's doing a sustained delivery of
an active agent. Not necessarily the active agent is being a you know, a control release, but it's some other mechanism that is helping you to control the release or control the solution of that drug and getting into the systemic circulation. And in the broader definition, that's how it falls into an implant classification, even if it is injected and not inserted. So that's what we were talking about earlier as well, and.
In the title of our panel discussion is why in the definition of why we want to actually use a bio material implant, so for reducing patient burden and improving the adherence. I'm curious, Aileen Eric, if maybe you can give some examples of use cases that are justifying the use of biomterial implants in your work.
Sure I can go first. My name is Eileen Sadly. I am a senior scientist that APPY. I work on a drug delivery and combination product. Just for introduction, The reason we use implant is for localized and control drug delivery, especially for hard to reach tissues in the body such as retinal diseases, as well as oncology applications. That makes the impluse super important.
Uh. Hello, I'm Eric Almquist. I'm the co founder and CEO of Pendent Biosciences. I have a little bit different perspective from everybody else up here. We are the drug delivery company that works with my colleagues here and as clients. So you know, from our perspective, we really are driven
by our clients' needs. So you know, from from most of my experience and creating these delivery devices, it's really driven by taking and existing therapeutic that's already commercialized or on the market and really improving the patient experience or the provider experience by by delivering a a more efficacious dose or longer lasting dose.
I have one example or use case or an area where actually it kind of really kind of showed like where implants can significantly benefit, and this is an ocular drug delivery to back of the eye. I think some of you might know that at one time there were really no drug products for the back of the eye, and at that time, if you had an infection, they would basically give a systemic antibiotic or oral antibiotic, but very small fraction of that goes to the back of
the eye during the AIDS epidemic. There were this CMB infections in the back of the eye and folks were losing eyesight. At that time, they were using some of the anti viral agents systemically, but a company developed an implant which would be implanted into the eye into the
victory as known as vitrosert. But it was a fairly large implant, and slowly that company developed another next generation, Reticert, and then Medidior, and as it kind of evolved, it became which was an implant which was to be inserted into something which can be injected. So the definition gets blood. But why do we do that? That's because you can't
really do frequent injections into the eye. The best you can do is once a month, but you can't go as So the idea was to kind of have an implant which can deliver the drug for more than a year a year to three years, and so that's the driver one of the really good example of why implants are needed for certain conditions.
Yeah, I think I've also worked in a molecular drug delivery, and I think going from that example, one of the most beautiful examples I've seen is this refillable port delivery system that was commercialized by roch Genentech, and it's interesting reading all the papers about that and seeing the presentations, like how many iterations and how many problems there were
to solve. And I think that gets to a topic that we've discussed prior to this panel, which is that developing these long acting implants or injectables can be very complicated, and anyone who's worked in that field sort of sympathizes with each other about that process. And I'm curious to hear from the panel what is it that's complicated or difficult about developing a long acting biomaterial implant.
So I think classically, from an implant perspective, you don't want the implant to be intrusive or physically to beg so that means that implant, when you design an implant, the drug has to be very potent. It's better also if the drug is a long half life, and so I think portent to the drug is important. Secondly, finding the right material for the implant and the right design of the implant asually, to be honest, there are very few materials which can be used in implants, and we
can talk about that later, So that's kind of thing. Secondly, it's sort of a design not just the formulation but also the design of the implant, which requires bioengineering principles. So it's a very challenging you know, design from a first in man implant is well, it's almost has to be commercializable.
I think, you know, maybe it can relate to everybody. So because you guys are here at the last you know, panel discussion, and the biggest trait that it needs is the patients and these are long acting delivery systems and it needs a lot of patients during the development. So the design factory is definitely one of them, which is you know, highly challenging because you're looking into the drug factors, you're looking into the excpient or the biomterials that you're using.
And then the second part is the process that comes in, and the process is equally challenging, and the patience comes in because now you're looking at the clinical development of these implants and then you're going to test the patients of the organization as a whole, because you're not looking at just uh, the developability of that, but you're looking at the clinical outcomes coming from that and how long an organization can can sustain in that competitive space to
you know, be patient with you and say, okay, keep doing what you're doing, even though it takes long time. There are a lot of values behind it from from the market perspective, but the patients is a key thing that many times we see a lot of challenges and difficulties.
In these developments.
Yeah, just to echoat, I think one of the most important problem we face, usually especially for chronic diseases like inflammation in the eye retinal diseases is basically balancing between the release profile and the material degradation. You don't want to have and people get multiple injection for chronic diseases, you don't want you want to factor that in. You don't want to have multiple implants in their eye. That
becomes a burden. And secondly, as it was also mentioned, is that it takes a long time for making an implant, and especially degradeable implant, one of the requirements is to show the degradation. And these days with competitive landscape, if you want to have like six months or one year even delivery, you should show that degradation, which usually takes longer than the release profile. So that makes the timeline very long, and that also makes you wonder about the competitive market.
So from the other side of the table, by the time these guys come to us, that means they've already tried the traditional technologies, the plgas, the standard materials that everybody is very familiar with.
So we get all the hard stuff.
So we're subject subjected to the market shifts the interests of our clients. You know, it was maybe small molecules ten years ago, fifteen years ago.
Now it's biologics.
So our challenge is to fit find the solution for the target product profile we're presented with and make something work in a time frame that's that's reasonable for our clients to continue moving forward.
Otherwise the market shifts again.
So given how long it can take to develop some of these products, do you have any suggestions from your own experience on what you could do to streamline, Like what should you do? What should you do early on because you don't get as many shots on goal when you're cycle the time is multiple months. What has been successful in your experience or in hindsight.
This really I mean, I think there's no single part, but I think ideally you know you what you want to take into the first in human or first in patient study is sort of a commercializable truck product because in this case you won't be able to establish bio equivalents that easily because if it's a local implant, if it's a systemic implant, yes you can do bi equivalents,
but it's risking right because there's high variability. So whatever you need to do in terms of design, in terms of pre clinical work, in terms of peak and safety, you want to do it in the right model, animal model, Get the right design, and then kind of make sure that you have good line of sight as to can you can you scale up the process, Is it going to be robust? Is it going to perform appropriately before
phase one? Probably even the ideal you would want to wait for an oral solid I would wait till phase two be but in this case you will have to do it ahead of time. Now that's not well received by the asset team because they would want to go fast, and so that's where the challenge occurs.
Yeah, I certainly echo that, and I think to Sean's to Erx's point as well. You know, the broader the TPP in the beginning, the better it is, because then the scientists and the development team has more room to come up with a narrower scope as they go, and this progress and all of these factors that Jamie just mentioned over the period of time, you would be narrowing it down as you go more closer towards the final product, but not necessarily.
You know you're you're going to define.
At that point, you probably have the definition and vision way ahead of your products. So even when you have your TPPS, you probably have the vision of the product that you want to deliver to a patient. So in terms of your final presentation, but in terms of that development pathway that you know, you go with the broader scope and then you kind of narrow it down as
you go. And then next part of that is they're taking an incremental step of success and not jumping through because many times you see this that you know probably end up taking a bit more risk than it's required and then end up having a more challenging situation because you know there's a study which needs to be done from the feasibility point of view, but it's it's it's not must, it's good to have, but sometimes skipping something like that can become far more challenging down the line.
So having that kind of very methodical approach in this overall development, going step by step, and then when you go from that translation from pre clinical to clinical, that would significantly improve the confidence of the product. And then that's how you probably see better success with that.
Just to add to that, one thing that we learned along the way is, as you mentioned, also not only having the right animal model would help a lot showing efficacy, but also the right model for the adverse events, like even inducing them into animals and having the true exhaustive basically all the experiments that can be done to induce that and to see how that adverse event can first in the first place, show up even in the smallest number of patients, just to know about it and just
to have an idea if that's going to be a problem later on.
For us, it comes down to two things.
We need very clear communication and direction from our partners. We are not the drug experts. We don't know as much about the API as you guys do. And any other thing, of course, is the financial support. You know, we we can move as quickly as our resources allow resources allow us to. So you know, we have many different options available to us, and you know we can go slower, go faster.
So I'm curious what sort of gaps in biomaterial or implant or long acting injectbal technologies do you all see that leave you wanting more like that you would look for startups or other companies to be developing for your next project or your current project.
Well, the one thing which comes to my mind is the material, the components of the implant, and you could classify them as metallic or the polymeric, right, And if you look at polymeric implants, either institute gel or the pre formed implant, PLG is kind of like the standard polymer which everybody uses because it's well characterized, safe, etc. And I remember that there were a lot of other polymers evaluated and has been studied, like caprolacton, polyarthesters, polynhydrites,
but unfortunately none of those polymers have kind of reached the stage where they have become sort of like a standard alternate to PLGA. And so I think there is a gap in terms of having new biomaterials which are as safe compatible like PLGA, which perform as well. And PLGA is its own issues in terms of the diffusional release, the erosinal release, and not ability to control release as well, and for metallic implant also there are limited choices and
limited companies which have the ability to do that. So I think those are the things which I think I see as one of the gap into the materials available.
Yeah, I think PLGA came maybe in early eighties or even earlier than that. But after that, if you see any biodegraded polymer which is approved by the FDA for any pharmaceutical application is very less especially an injectable space if we talk uh and certainly I think that is one of the key challenges to have a suitable biocompatible material and if possible a biodegradable material for an implant delivery, that would definitely make it more appealing, especially for the pharma.
Companies to go and try these things.
One of the challenges possibly in that one is the excipient approval pathway from the regulatory agency can be you know, a chicken and egg kind of a situation, whether you know who would be the first one to go and then try that out and and do that. But there's a lesson or multiple lessons to be learned from a device side and a device industry, because they have been quite successful using different biocompatible materials metal or non metal UH.
And I think some kind of a cross collaboration between a pharma company and a device company can be really helpful in that and in that space to come up with those injectable you know, implants and more suitable biomaterials to be used for this kind of application for drug delivery.
Yes, material is definitely one of the biggest gap. There is only a handful of them that has been have being tested so far, and it's mainly p g A that people use in the industry. And also one of another bigger gap that I can mention is implants for biologics that it's very hard to develop, especially with the degradable implants, and that's another area of interest. If can be developed into degredible implants.
Make them as a surprise. I'm going to say materials as well my shameless plug here for self promotion. You know, from from my experience UH independent, we have seen a significant s gift and the openness UH for our drug partners.
To be interested in alternative materials.
I think the interest in hydrophilics and large molecules is largely driven that. As much as we can twist and poke and prod PLGA. Sometimes it's just not going to work and UH and I and we do see a shift in the in the willingness of our partners to be open to new materials.
And I second that maial new materials for formulation with biologics is something that we look a lot for as well, not only for compatibility with the biologic and giving the sustained or release profile you want, but also having the ability to potentially, you know, sterilize. How do you sterilize these? And you know, we we hate doing a septic manufacturing, but it's almost the only option if you're working with
any sort of particulate or implant. So one thing I've always been on the lookout for are long acting solutions for biologics that are like an in situ, in situ forming depot that maybe you can sterile filter and UH and get the right balance of release no burst, long release, no burst, and good tolerability. So that's on my wish list. Reach reach out to me later if you have something in terms of yeah, what about what about like device
like implantable devices sort of deep refillable depots. I mentioned that this this like a port. How about applying those to other tissues or other sort of devices that have a sort of smart, sort of mechanical release. Any have any of you looked at those.
So my so I I haven't really worked directly with them, but I know that for ocular applications that have in several implants designed. One is the port system which you describe, which gene and Tech developed where you could refill it. There was another delivery system which was like a micro electrical mechanical system where you actually was electrically driven pump to pump the fluid into the vitreos. But also I've seen papers and some work on pumps for bringing delivery local,
localized delivery to the parts of the brain. Those are very you know, unique examples.
I haven't.
I don't have experience working with them per se.
Yeah, I think limited experience in that space. But but you're looking at instead of having a passive chemical based diffusion based system, we are looking at a physical stimuli coming in either an electrical uh, you know, signal or something like that. And I think there are a lot of you know, probably a couple of areas, the therapeutic areas, maybe the contraceptives is one of them, where we have
seen some of those applications, especially with metallic implants. Hope to see a lot more on the type one and
type two diabetes space. We have just had that amazing discussion right before this one, and seeing something in that regard, I think either I think, just continuing to that wishless part is if a metallic implant or a biocompatible implant is inserted and if it is refillable, then that that takes a lot of these design and then formulation challenges off the table and possibly it can provide a much longer delivery.
So something to look for.
We have about five minutes left. We could open the floor to the audience if anyone has any questions for the panel.
Hi Stephen Russell, Chief clos Circuito Bionics. I think for me, it's pretty obvious if you have a localized delivery problem, why an implant would be a really good option.
But for more systemic delivery.
Now that we have so many drugs at least in my diabetes space, like GLP one agnes that are given weekly, and there was a recent failure of an implant to give a GLP one in tarsia that wasn't approved, what are the specific circumstances where you would want an implant to give a drug systemically as opposed to.
Locally.
Yeah, I think in my experience what I'm aware of is and systemic. All say it was primary to reduce patient burden, right adherence. One of the oldest implant is the zolax implant by Estra Zeneca, which is like a very small implant implanted using a broker. And then there was an implant being developed for prosted cancer where it was like a long duration I think duration is imported.
At one time one could not have assumed that you could get a long acting in the injectable that will work for six months or provide sustained pKa profile for six months. But now there are several process once every three months. Then the question is do you really want to design an implant in that condition? For systemic You're asking the right question.
I think the contraceptives are pretty a good example where systemically acting implant could be used. And we talked about the broad definition of an implant from USP, so like the anti virals, those are also systemic. So I think it just depends, I know, from our perspective, or depends on that on the application. I think a long acting non implant we I usually like to think they're probably easier to manufacture and than a solid form.
Yeah, well, the long acting injectibles typically the the design comes on from the API. How do you design the API to right solubility and the right PK characters characteristics in the implant? It's more forgiving, right, It's really the design of the implant which controls released, not the API. So there's a different ways in which you look.
At this, maybe a slightly different perspective on that. I think necessity actually was a key driver in that when when Jamie talks about Gozarelin or Soladex implant or lhr H when they came in the early eighties and nineties, the shorter half lives actually kind of pushed the industry and said, we have to make something so these patients don't have to go through the burden of multiple injections in a day, which was almost impossible at that point.
And as it grew it people understood the application and benefits of a long acting injectables and implants, and it kind of widened it reputic areas. Over the period of time, we saw the emergence not in an endochronology uh and uh, you know, in which mainly with the large and ghrge analogus. But as we grew further, we saw like this could be a very beneficial when you have patient therapeutic adheren such an issue. So that's where the you know, all of the C and S drugs came into the impact.
And then now we saw the chronic administration and then drug design and that's where the viral anti viral drugs started coming in. So we are seeing more and more chronic application with the systemic circulation.
With these kind of drugs.
And I think it's more about at what point the industry would decide that this is a chronic administration and an implant or a long acting can be really helpful, thank you.
I think also it really depends on your molecule and it's you know, it's it's safety profile. So like if youse, you know, slap an FC or lipid on a molecule and it's active, then you if you don't have a sustained release, you'll get a very high SMAX you could have toxicity. So in some of those instances, having a sustained release could give you could allow you to get the best best of both worlds, long acting and good tolerability.
So some indications like antipsychotics also benefits a lot, and more recently for low income countries, vaccine application for multiple doses that would release all those adds up to the important stuff.
Long acting and how do you reverse it if it gets too high? All right, Thank you everyone, and thanks to the panel. Thank you, great discussion.
Thank you.
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