Trends And Advances In Inhalation Delivery With Kindeva's Stephen Stein

Stephen Stein, scientific director of inhalation products at Kindeva, joins Supplier Horizons host Tom von Gunden in a discussion of opportunities and challenges for inhalation product development. The topics discussed include ensuring bioequivalence in generics, reducing environmental impact from propellants, and advancing inhalation-based delivery of vaccines and combination therapies.

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Episode Transcript

Tom von Gunden, Chief Editor, Drug Delivery Leader:

Welcome to another episode of Supplier Horizons, the series in which we hear from suppliers of products and services to the drug delivery industry about trends and opportunities they're seeing in the patient and therapeutic landscape. My name is Tom von Gunden, Chief Editor at Drug Delivery Leader and your host for the series. And today I am joined by Stephen Stein, who is Scientific Director of Inhalation Products at Kindeva.

Welcome, Steve.

Stephen Stein, Scientific Director of Inhalation Products, Kindeva:

Thanks, Tom, for the opportunity to talk today.

Well, it's my pleasure having you. Thanks for joining.

So obviously, as scientific director of inhalation products, the topic for today will be the inhalation route of the administration around formulations and devices in that area. I know from a previous conversation we had that one of the trends that you're addressing there is the increasing demand for generics. And so, can you tell us a little bit about how that space — what comes to mind in that space as it relates to inhalation products?

There definitely is a desire — I think from everyone — to have increased availability of lower cost inhalation products to expand the access of people who can afford these important medicines. We, Kindeva, have been doing some work in that area [generics]. And it's actually more challenging than I might have thought when we began doing that. Essentially, just like any other inhalation product, you need to do a lot of work to demonstrate that you have a stable, efficacious product.

So, there's all the additional work that you do on any drug product, but it actually turns out to be a little bit more challenging in some respects because you need to demonstrate what's called bioequivalence to the product you're making a generic of. And that ends up being quite challenging.

For example, we recently developed a generic inhalation product, and there were over 50 different metrics that we needed to demonstrate bioequivalence to. So, it can be quite challenging to develop it. Now, obviously, you have the benefit of knowing that the drug is safe and effective. So, that's obviously a great benefit. But there are many technical challenges that need be overcome during development of a generic inhaler.

Yeah. I'm just curious: When it comes to the bioequivalence and the regulatory scrutiny around that, how much, if any, leeway do you have at all in terms of device design when it comes to matching, so to speak, what's already out there?

Sure. In some respects, you need to try to match what is called the user interface. So that essentially means that, the patient, if they've used what's called the reference product, the branded product, while the inhaler might have a different color, maybe a little bit different shape or some differences, it needs to be similar enough that they're going to know how to use it without making mistakes.

So, there is some leeway, but in some respects, you need to have it be quite similar so that there won't be any confusion.

Gotcha, gotcha. Well, thanks for the coverage on that topic.

Let's move into another one that you and I briefly discussed in preparation for today. And that is the area of sustainability or environmental concerns. And I know you talked specifically about the need to address some of the issues and opportunities around propellants. Let's just go there and get your thoughts on that.

The propellants that are currently used in metered-dose inhaler products have a relatively high global warming potential. So, there's a desire from a sustainability perspective to identify propellants that can provide the necessary properties but have a lower global warming potential.

So, there's been a lot of effort in this. The amount of propellant that is used in pressurized meter-dose inhalers is pretty small, overall. And yet, these propellants are also used in things like air conditioners or refrigerators, so large industrial quantities of these propellants are used and manufactured. And then to use them in an inhaler, they go through additional purification steps. And so, we're able to leverage the mass production of these current propellants. And then, we do the extra purification necessary.

As these propellants are removed from the market for air conditioning and refrigeration, just the economics of things are going to become challenging. And so even though the overall amount of propellant use is not really a huge issue from a global warming perspective, we really do need to transition these propellants to maintain the financial viability of the products. And also, any little contribution we can have to reducing global warming potential and   emissions is certainly desirable, as well.

It turns out there are a lot of technical challenges because, for inhalers, the propellant really makes up the vast majority of the composition of the formulations. Sometimes more than 99% of the formulation is a propellant. So, it is a substantial change. And so, there's a lot of work we have to do to ensure that we can get equivalent efficacy and product performance with our propellants as we go to these green propellants.

That sounds good. I'm sure that the audience joins me in the appreciation for the work being done in that area.

So, we've talked about the work around generics and sustainability. Anything else, Steve, front of mind for you when it comes to advances or innovations in addressing patient needs or therapeutic areas and challenges or opportunities there? Anything else?

Sure. Certainly there's always a desire to identify new drugs, maybe different types of drugs, different mechanisms of action. There's work in early development and actually clinical development of drugs that will potentially provide a therapeutic benefit.

One trend in recent years is to put multiple drugs in the same inhalation product. If you can avoid having a patient need to use multiple inhalers, that's a benefit. And sometimes, the combination of the drugs can actually provide a synergistic benefit that is actually better than the two separate products themselves. So, that's another area of research and ongoing development.

One kind of looking outside the box: [The] inhalation route can be useful as delivery for vaccines, particularly in developing markets, parts of the world that maybe have some infrastructure challenges. Many vaccines need to be refrigerated until they're used. And that really is a huge barrier to access of vaccines in some of these developing countries.

And so, there's been research doing some spray drying type[s] of technologies that can provide vaccine stability at room temperature. So, you can get rid of, for example, the requirement for what we call the cold chain, just keeping the product refrigerated until use. And that could potentially open up markets to have vaccines that might have challenges doing that. So, that's an area of delivery.

And there are other things, like just making the products easier to use for elderly patients or young patients. So, lots of areas of potential innovation. And I think we'll see some of these benefits being realized in the market in coming years.

Great. And there's a trend that we monitor in various routes of administration, and that is the move toward accommodating larger molecules — large molecule biologics in convenient devices. So, anything to say about the challenges and opportunities on that front when it comes to inhalation?

Yes, that is definitely an area of research in the inhalation delivery system. So, some things: There are molecules that may require higher doses than can be delivered with your typical metered-dose inhaler or dry powder inhaler. So, people are looking at developing high-dose, dry powder inhalers, maybe aqueous systems such as nebulizers, that can deliver higher doses.

And then as you mentioned, yes, some biologics that traditionally may have been delivered via injection or just haven't really been studied yet. There's a lot of research using the inhalation route to deliver molecules like this, [with] potential benefits like if you can avoid a needle. There's certainly a benefit. A lot of patients would rather take inhalation of a product than an injection. So, definitely, that is an area of research in our industry. And we're going to be seeing those products reach the market in the near future.

Great, great. Well, I like to wrap up by just opening it up to how you see things as you look toward the future. So, anything to add about hopes and dreams and potential changes in the patient landscape as advancements and innovations move forward? What might the health and lives of patients be like should some of these things come to fruition?

I definitely think there's lots of room for improvement. One area we have discussed is just improving access, whether that's through availability of generics or maybe molecules that could be delivered a little more simply in parts of the world where infrastructure is limited. So, that certainly is going to be an area where I'd love to see benefits there.

There are even things like connected inhalers, where you can get feedback reminders to take your medicine. Or caregivers might have access to information to ensure that the person they're caring for is taking their inhaler correctly. So, I think there's certainly room for additional innovation to make sure that we can continue delivering and potentially open up areas of access and benefit to other patients.

Yep, well, sounds good, Steve. I want to thank you for joining me for this episode of Supplier Horizons. And I also want to thank our audience for joining us as well, and we'll see you next time.