Investigating Inhalation Forms and Drug Delivery with Shabbir Mostafa (DCAT Week)

Shabbir Mostafa, head of Business Development — Advanced Delivery Systems, Recipharm, sat down with Grant Playter, associate editor, during DCAT week to discuss the current state of inhalations forms and drug delivery. The full interview transcript can be read below.

Broadly speaking, if you had to isolate one overwhelming drug delivery trend, whether that's in development, regulatory approvals, or even commercial markets, what would you say is the most impactful at this moment?

Shabbir Mostafa: I think for inhalation in particular its sustainability. So at the moment, we, within the metered dose inhaler (MDI) marketplace, use propellants for the user, for the formulations. And these propellants have high global warming potential. And now, these propellants have kind of been slowly phased out from the regulatory side. And they're looking to replace those propellants with low GWP, or low global warming, potential propellants, which are at quite an early stage in terms of their development.

But the environmental, the carbon footprint isn't going away. So there's a real problem at the moment of changing, of moving from high GWP to low GWP propellants. Because the expectation is it's going to be a lot of cost in terms of your development, your clinical batches, and also modifications to your facilities.

So, a number of the big companies that are big players within the inhalation market have already started to move over and started to transition. But there's a lot of other companies behind at the moment that haven't transitioned yet, and are looking to see what the regulatory side will be in terms of what they will have to do as they move across. And so it's quite an important area within innovation, because it's such a large market.

Just building on that a little bit, you say the low GWP are early in development, and some companies are beginning to transition. Can you expand on that, do we have any sort of timetable?

Mostafa: The phase down is starting to happen now. The high-GW propellants — the products that are currently used today in formulations — they're going to be transitioning sort of to a lower point. They can only sell a certain amount, as it goes. And it's a step down process over a number of years, so by ‘25, ‘26, the amount of propellant available will be very low.

The proponents are used in lots of different markets. And actually in the medical side of it, the medical use is very low, but there was an exemption for medical use for these propellants. However, that exemption has been now taken away, so this step down process is now affecting also propellants for the medical use as well.

Are there any other sustainability measures you want to highlight, anything you can point to as a big trend?

Mostafa: I think everything comes to sustainability. So they look at the carbon footprint of the factories. Are we doing things like solar power, how are we doing recyclables, etc. is huge. Actually, within Recipharm, in general, sustainability is a huge, huge area, we have people dedicated to that to look at how we can get become a net zero company. So it's huge within the pharmaceuticals.

Can we talk a little bit about like nasal delivery and just broadly inhaled biologics, what's going on in that space?

Mostafa: So nasal delivery, I think, is becoming more and more popular. Traditional nasal delivery was multi-dose delivery, just your normal nasal spray that you'd use for anti-allergies, etc. But now as you've probably seen, there's what we call one shot unit dose delivery devices, which basically shoots one dose into your nose, and that's been used for things such as rescue medicines and immediate pain relief.

As Recipharm, we've developed a device for single-dose delivery, and it's going to be used in those areas, and as you know, with rescue medicines — its for people overdosing on things like fentanyl — so they need to have this straightaway rescue medicine. Just gives you one shot and you get hopefully relieved from the overdosing of the fentanyl.

What are some observations you’re seeing in terms of inhaled biologics?

Mostafa: So, from an inhaled biologics side, we're starting to see more and more customers looking for that development. There's two areas which you can go in; the biologics one is either a nebulizer or dry powder inhaler. But the nebulizer, which is a solution, it tends to be quite high-shear, so it can destroy the large molecules as it's being inhaled. So, there's a challenge using nebulizers for biologics.

We've developed a soft mist inhaler, which is one of our newest devices, in partnership with Medspray, where we have a company called Resyca. This soft mist inhaler is very gentle. And we're working with a number of customers biologics, large molecules, for mimicking of the nebulizer route.

The other preferred route is through DPI, dry powder inhaler, where you can spray dry your active or your biologic onto something, a carrier. And that's starting to show some popularity now. The issue with DPI has always been reproducibility. And so that's the challenge with inhaled biologics at the moment, making sure we still get reproducibility of the active.

From a development perspective, can you talk about some of the considerations that go into selecting a drug delivery system? Like what's the discussion when you're selecting between like, say, a nasal inhalant versus an inhalant one would use for asthma?

Mostafa: So asthma disease is straight into the lungs, so it's looking for respiratory delivery, so you would use an inhaled, so either an MDI or a DPI delivered, or a nebulizer delivery. If you are looking for something for an immediate sort of pain relief in the head like a migraine, you'd probably go through your nasal delivery, because you've got the delivery faster.

Pfizer just had the migraine nasal spray approved the other day, I believe. [Editor's Note: This interview was recorded on March 18th, 2023.]

Mostafa: Yes, it has been, Pfizer. So that's why I'd say the difference is, if you're looking for a sort of respiratory, you'd go inhalation; if you're going for nasal things like pain relief, or as I said, rescue medicines, etc., for the nose to brain delivery.

Can you give me a bold prediction for the future of drug delivery five years from now?

Mostafa: I think the market for inhalation is definitely going to change. I think we're going through this huge change, as I said with the MDIs, we don't know where that's going to be in five years' time, whether there actually is going to be a business for it, or whether everything is going to transition across the DPIs.

My suspicion, I think, is that there's going to be a hybrid, I think there'll be less of MDIS and I think there'll be more of DPI formulations out there in the marketplace. We, part of our business is huge, is MDIs and valves. So we still see a value for it, but we don't know what the market will be like because of the transition from high GWP to low GWP propellants. We don't know what the market will be like in five years' time. So I think that's the big thing for us. And looking at that and seeing where, you know, what will happen in the future.

What about ten years?

Mostafa: Ten years? That's difficult. I think that it'll definitely be the growth of inhaled biologics, I think, over a ten-year period. I think that biologics will be a lot more in the next five to ten years. I think for nasal delivery, again, I said it went through the uni-dose, so single dose shot for things such as rescue medicines, and it's quite big in America, in Europe, etcetera requirements. So that's where I see the market in ten years' time.

For more of our coverage on DCAT in 2023, viewers can visit this page.