Episode 5: pMDIs & Sustainability

John Price (00:16): 

Welcome to Coffee with Kindeva, a series of thought-provoking conversations about complex drug delivery. Today, we will be talking with Louise Righton about the role of sustainability as it relates to pressurized metered-dose inhalers. I’m your host John Price. It’s my privilege to host Louise Righton on today’s episode of Coffee with Kindeva. Louise Righton is global strategic marketing leader for the inhaled drug delivery business at Kindeva. She has worked in the pMDI sector for 17 years across marketing and government affairs. She is a board member at IPAC, the international pharmaceutical aerosol consortium, where she advocates for the pMDI as an essential drug delivery device in the management of lung disease, working to ensure that global environmental policies relevant to inhaled therapies, appropriately balance patient care and sustainability efforts and objectives. She works closely with the R&D team at Kindeva to promote the use of sustainable technologies in Kindeva’s new product developments. 

John Price (01:20): 

We’ve got kind of a pertinent topic here today around some of the sustainability efforts going on, especially within pMDI, and some of the policies that are going on. You recently wrote an article on drug delivery, this is kind of based around that. We’ll have a link to the article below in the description for those who want to reference that. But I thought first, maybe we go into some of the, just kind of get us level set here with where and why these changes are happening. I understand that we went from a CFC-based propellant back in the ’90s and transitioned to an HFA propellant. Is this similar? I mean, are we kind of facing the same thing if you want to speak to that, that’d be great. 

Louise Righton (02:01): 

Yes, John. Absolutely. So what we are seeing now is as a result of climate change, which obviously, you know, we all want to address and the pharmaceutical industry is no different from other industries in wanting to be, you know, responsible and wanting to move to be more sustainable. So what we are seeing now is a focus on what we call the HFC or HFA propellants, and they’re basically F gases. And we are seeing a focus on wanting to transition away from those to more sustainable alternatives for the propellant gases that we are using our metered-dose inhalers. So the current F gases that we are using, were actually as a result of previous transition. Back in the day, they were seen as the green alternatives to CFCs, you know, back in the ‘80s, we’d got the hole in the ozone layer. 

Louise Righton (02:53): 

We got the Montreal protocol, the global protocol addressing, you know, substances that deplete the ozone layer, ozone-depleting substances. And so this industry has already gone through a transition to greener and more sustainable alternatives. But now of course, with the climate change crisis, we need to do more. And so now the F gasses that we are using now need to be transitioned to even greener alternatives with lower global warming potential. And so with that in mind, we are seeing F gas policy in Europe, in the UK, you know, in the US as well, being reviewed. And there’s a lot of encouragement and a drive for several industries, including the pharma industry to transition from our use of the current F gases that we are using to green alternatives. So that’s, what’s going on here. There are other policy changes happening around sustainability in pharma, but the one that concerns us as a big MDI manufacturing supplier is this one, it’s the focus on the F gases that we’re using. 

John Price (03:58): 

So, obviously Kindeva has only been around for a year or two, and I guess we’re coming up on two years here, but people actually in Kindeva have been through this change before. This isn’t new to us. I mean, we have people who actually worked on the previous change from CFC to HFA, is that correct? 

Louise Righton (04:16): 

Absolutely. John, we are so lucky to have such a wealth of knowledge and expertise and experience of course, in our company. So yes, our previous owners 3M were at the absolute forefront of the CFC to HFA transition. And our particular division, we used to be called 3M drug delivery systems, we were at the forefront of this transition. Globally, we were one of the founder members of IPAC, the international pharmaceutical aerosols consortium, which was formed so the industry could collaborate to move away from CFCs to the greener propellants. And yes, we were a leader. We did register and launch the world’s first CFC-free metered-dose inhaler back in the early ‘90s. And yeah, very, very pleased that several of our scientists and regulators that worked on that project are still with us today and contributing to the new transition with all of that experience and all of those relationships with the regulators and with the environmental agencies worldwide as well. So that’s good for us to know that we have that experience that we can call on and we’ll be a leader again, in this new transition. That’s absolutely our goal. 

John Price (05:31): 

That’s great. So now I want to kind of move in to get into the article, maybe give us a little background because I think there’s some specific UK policy that’s being proposed, or you can kind of tell me where it’s at. I’m not familiar with UK politics, just being on the other side of the ocean. But I know sometime this year there was a push to transition away from pMDIs to DPIs. Just give me a little background on what that policy was and then maybe we can start to talk about, you kind of covered six myths in this article and we can kind of go over some of those. But at first I, I kind of want to understand what the policy or at least the proposal was in place. 

Louise Righton (06:13): 

Well, it’s something that I feel quite strongly about out John being a pMDI advocate, and knowing how many patients re really rely upon the pMDI format and what I observed, not only in the UK, but in some other European countries as well, is that the pMDIs seem to be getting a bad rap. Okay. So, you know, health systems and governments want to decarbonize, and we absolutely support that as a company and we want to embrace that and do our part to drive that and support that. But what we were seeing happening was in several countries, and let’s take the UK as an example, the national health service put out a policy a couple of years ago, in fact, and said, we don’t want to wait for low GWP pMDIs. I think there was some disbelief that the industry was actually acting. 

Louise Righton (07:06): 

We don’t want to wait for those. We want to do something fast to start to decarbonize the inhaler industry in the UK and the treatment of asthma and COPD in the UK. So this is just an example of a policy, but this was quite a key one. So some targets were set and some incentives were put in place for prescribing physicians for GPs, as we call them general practitioners in the UK to begin to initiate new patients onto dry powders rather than pMDIs, and to switch where clinically safe to do so. I must say that it’s not been sort of switch at all costs, but where clinically appropriate to do so to switch patients to a low carbon inhaler. In this case, it’s a non-MDI inhaler. And so that policy was in place for all of last year, and then this year in October the bar was raised and the targets were set even higher to encourage GPs to move more patients away from MDIs and into other alternatives, which tend to be dry powder inhalers. 

John Price (08:12): 

So maybe I’ll jump in here. So, we’ve got a myth here from the article that for most patients the DPIs are more effective than the pMDIS and patients prefer them. Is that true at all? 

Louise Righton (08:28): 

Thanks, John. Yeah, that was one of the myth that I address in the article. And I would say, many of the proponents of this pMDI to DPI switch method of decarbonizing the inhaler market will often selectively cite studies that seemingly prove that dry powder inhalers are more effective than pMDIs that patients find them easier to use, or that patients prefer them. And what I would say is that for every study that shows that DPIs are more effective and patients prefer them, there’s another study that shows that pMDIa are more effective and patients prefer them. So I am certainly not here to say the pMDI is right in all circumstances, the pMDI is better, that pMDI is right for every patient. That would be wrong of me. But what I am saying is let’s take a balanced view. 

Louise Righton (09:22): 

So I have seen a lot of the explanation behind this switch policy coming from just one or two studies being cited. And what we would say as Kindeva, and indeed what we have done through this article that I’ve written, is say look at the breadth and the wealth of the literature here, look at all the studies, look at the meta-analysis, look at the literature reviews and take a view. And actually what that view tells you is that there is no preferred device. There is no one size fits all. Some patients find a pMDI better, easier, more effective and prefer using it. And others would say the same about a dry powder. So let’s not be one sided about it and selectively cite studies that support a particular way of thinking. Let’s take a balanced view. That’s my thoughts on that. 

Louise Righton (10:14): 

I think to pigeonhole the pMDI and say this is only suitable for delivering salbutamol, the short acting beta agonist therapy, would be a mistake and would really deprive many patients from a format that they have used maybe their entire life, they find easy, find effective, and they don’t want to switch from. So, as I say, I think the evidence is there in the literature, look at all the references, take a view, but let’s make sure we take a broad view and we’re not just looking narrowly at one or two studies to support a point of view. 

John Price (10:52): 

How about, do you think patients have a right to be made aware of the carbon foot print that their inhalers or their medicine might have before they’re prescribed whatever the treatment is? 

Louise Righton (11:05): 

I think personally, my view is that we need to be very careful about this. Now, patients need to be informed and involved in the decision making about their treatments. Of course they do. And I don’t think that anyone would advocate otherwise, but we need to be very, very careful because when we saw the inflammatory headlines in the UK, was it the summer of 2020, we saw some headlines that had come from a paper that had been written, which said, “using your inhaler is as bad as eating so many burgers or driving from Sen to John or whatever the stats were that were being used. And this resulted in a backlash in social media, from patients. And they said, wait a minute, I’m using this product because I have to, it’s helping me control my condition and it’s saving my life. 

Louise Righton (11:55): 

And I do not want to be made to feel bad about that. So I think yes, by all means, let’s make patients aware, but let’s just be careful and not be sensationalist and not make patients feel bad about using their life-saving medicine. The global guidelines around asthma management and COPD management, you know, the gold and other guidelines. So it’s very, very important to involve the patient, but it’s very, very important to match the right therapy and the right inhaler type and device to the patient. And what we mustn’t do is have patients losing confidence in their treatment, being scared to use it and stopping using it because that can have very severe potentially life-threatening consequences. So if we’re going to communicate to patients about the carbon status of their inhaler, we must do that very responsibly and avoid the sensationalist headlines. 

John Price (12:55): 

Makes sense. So, I’ve also seen that a minority of patients, some young children, are unable to use DPIs but the majority of patients find them easier to use and require less coordination than a PDI, leading to greater adherence. I’m assuming this kind of goes back to the first point, but maybe speak more or specifically around coordination between the two. Again, there’s probably a plethora of studies out there showing data on both sides, but I’ll let you speak to that. 

Louise Righton (13:23): 

Yeah. Thanks, John. Anyone that works in this space right in asthma and COPD management, they understand how challenging it is to get patients to use devices correctly and to adhere to their treatment. It is a disease state that is characterized sadly by poor control and by patients struggling to use these devices, beacusr many of them are not straightforward. What I would say is that, there is evidence and there are studies that just as many, if not more, users of dry powder inhalers struggle with technique than do pMDI users. And you know, one particular study says 94% of dry powder users and just 74% of MDI users make mistakes when using their devices. Now nobody’s happy with 74%, okay, but we certainly shouldn’t be advocating that everyone switches to a device where 94% struggle to use the device. 

Louise Righton (14:23): 

It’s really important that patients get some consistency in their devices I think this tells us because we know it’s time consuming to train patients, and really you only want to have to train them once and then check their technique and then hopefully achieve some consistency in the way they’re using their devices. The issue with dry powders is that pretty much everyone is different. You know, you have reservoir devices, you have devices that need loading with capsules. There’s different opening, closing, twisting, all sorts of things going on with the use of that device. Whereas what we can say about a pMDI, although in some circumstances it can be challenging for patients to learn and use, what we can say is every single one is the same. So if you can learn to use one, then you can use any pMDI. 

Louise Righton (15:18): 

And again, this is why we advocate if a patient is comfortable and has learned to use a pMDI and feel confident in that device, then let’s leave them with that and not prematurely really switch them out of that for this sort of short term, carbon-led thinking when actually low GWP, low carbon MDIs are on the horizon. And we’ll talk about that shortly, John, but you know, we are less than five years away from the first ones being available. So let’s not throw the baby out with the bath water and take this device away from patients if they’re confident in using it. 

John Price (15:56): 

Okay. So, when we’re looking at kind of these different inhaler devices, the pMDI is really the only one that has an environmental impact from a propelling standpoint. Is that really all we should be looking at when it comes to sustainability policies for these medications? 

Louise Righton (16:12): 

It’s a great question. And the focus is absolutely on propellants, as you’ve heard. You know, we must take, again, some broader thinking because propellants are only a part of the story with regards to a product’s life cycle and it’s total environmental impact. So, whilst absolutely propellants are the focus, and as an industry, we have to transition to lower GWP propels and in doing so we will massively reduce the carbon footprint of the pMDI industry, and of the inhaler industry as a whole. We must also not lose sight of the that there are other considerations. So we have to think about, the amount of plastic that’s used in devices and particularly some of the dry powder devices. A recent study showed that once we move to the low GWP pMDI, then that inhaler with the new propellant in it will have the lowest total environmental impact for 10 out of 14 different categories that have been considered in a recent study whilst the DPI would be the worst option for 8 of the impacts out of 14. 

Louise Righton (17:28): 

So again, this is why we are advocating for maintaining the MDI market and giving the industry chance to transition to low GWP propelling because once we have done so in less than 5 years time, we will have an inhaler in our hands that is superior in general terms, across many, many more aspects of environmental sustainability as well. And we mustn’t think that once we’ve changed the propellant, that we’ve all done our jobs and sit back and congratulate ourselves because there is more to do on plastics on the use of metal on all sorts of the inhalers. So, we are working hard to, for example, design new dose counters that have much lower parts count, much less use of metal and plastic than the previous ones have. So we must all keep going and not think that propellants are the answer to everything. They’re the first thing that we’ve got to change, but we’ve got to keep going and we certainly intend to at Kindeva. 

John Price (18:35): 

Okay. So, you brought up a point there. I have asthma and I have used both pMDI and DPI. I see my DPI has a counter on it and I always thought that was nice, so I didn’t throw it out while there was still medicine left, but you’re saying that some pMDIs also can have a counter on them too, is that correct? 

Louise Righton (18:53): 

Yes, they do. And not every pMDI in every market yet has a dose counter on it, but it’s most definitely a trend John, because it’s great practice, isn’t it for a patient to be able to see, as you just said, how many doses they’ve got left so that they don’t carry on using it right to the very last drop because they might not get the right amount of drug if they use it literally until it’s empty and they’re spraying air. That’s no good, but also it’s no good if they throw it out too soon while there’s still some usable doses left. You know, that’s not very environmentally friendly either. So we innovated in dose counters many years ago. I think it was 2006, 2007 when we launched our integrated dose by dose counter to the industry. And I’m pleased to say that’s been adopted on several of our clients products over the years. It’s a robust dose counter. It’s an accurate counter and again, that’s one where we are innovating to take, you even more components and more plastic out of the supply chain. So yeah, I would say in the developed markets, the majority of MDIs now have a dose counter. So the dry powder device doesn’t have that advantage any longer over the metered-dose inhaler. 

John Price (20:13): 

Okay. So now kind of the last myth and, to me, this is kind of crucial. I think it gets kind of the heart of it. So, to decarbonize the inhaler market quickly, we need to just switch as many patients as possible from pMDIs to DPIs and reduce the carbon footprint as quick as possible. Tell me why that’s not necessarily the best approach. 

Louise Righton (20:35): 

Yeah, it’s a great question, John. And it required us to partner with another pharmaceutical company, friends of ours ke, who are a pharmaceutical company based in Gar Italy but with a very strong business throughout Europe and particularly in the UK. And we were talking one day and wondering really, if anyone had studied the impact of the NHSS policy to switch patients. And so we actually got together and commissioned an economic modeling agency called Frontier Economics to study the policy and to look at some different scenarios with regards to that MDI to DPI switch policy. And what the study found was that the policy to switch patients from pMDIs to DPIs is unlikely to result in a substantial reduction in carbon emissions because the faster you switch patients to non-MDI treatments, the faster you shrink the MDI market and the faster that takes away the market opportunity, the incentives, for the pMDI companies to invest in the innovation and in the production of these new low GWP inhalers. 

Louise Righton (22:00): 

And, we’re not the only people to be saying this. There’s been several pieces very recently, I would say in the last three to four months in the pharmaceutical press aimed at pharmacists in the medical press as well, aimed at prescribing GPS that are questioning policy. There was a recent PA in the BMJ, the British Medical Journal that found very, very similar that the right way to decarbonize the inhaler market is to switch both the non-salbutamol and the salbutamol market to low GWP pMDIs. And that that is the fastest way to achieve a decarbonization. And again, if we just take a proportion of the market, the non-salbutamol market, and switch that to DPIs, then that really imbalances the market and takes away the incentive of some of the players in the market to invest in the new green propellant technology. 

Louise Righton (22:59): 

So whilst on the face of it, the policy seems very well intentioned. We can see that, the policy makers want to take action. Let’s not wait for low G to P propellants. Let’s switch patients now to a lower carbon DPI inhaler whilst that on the face of it seems the right thing to do and is very well intentioned. What we find when we look a bit deeper into sort of how that plays out is that there are unintended consequences. You slow down the transition, you actually don’t make carbon savings overall because you delay the transition in the salbutamol market, you actually drive a cost to the NHS. And actually there is the risk of having a negative impact on patients as well, because there is literature out there that shows that if you switch patients from one device to another, for nonclinical reasons, carbon-led reasons, then a certain number probably in the sort of 4% region of patients will struggle or to control their condition will have an exacerbation and will end up in hospital. 

Louise Righton (24:09): 

And actually, if a patient goes to a clinical setting their carbon footprint rises exponentially and far outweighs any carbon saving that’s been made by switching their inhaler. So again, we are advocating for the bigger picture to looked at here and also for these health systems, such as the NHS to work with us, the industry, because we’ve decarbonized before we’ve moved before from one propellant to another, and we know how to do it, and we want to do it. So please just give us the time that we need to do it in a controlled manner is really what we’re asking for, John. 

John Price (24:46): 

Okay. I just thought of a question because when we did transition before I know it was over quite a while. It wasn’t like, oh, we’re going from CFCs to HFAs in a day. I think there were certain markets where they could just do that drop in transition. Maybe my refrigerator didn’t use CFCs anymore and they just drop in HFAs. This market’s obviously different in many ways from refrigeration, but it’s a regulated environment and I guess maybe speak to the fact that that kind of requires a certain amount of a forethought and planning. It’s not like we can just change over propellants overnight, it takes some science behind the scenes to make sure everything’s going to work as it did before and remains effective. Maybe talk about this regulatory process a little bit for me. 

Louise Righton (25:37): 

Yeah, absolutely. John and anyone that’s as old as you or I can remember the last transition, right? You just talked about your refrigerator. And I remember when hair spray had to move CFC free in the late ‘80s when we all had been there. So, there were some consumer examples that most people would’ve seen and would remember, but yeah, I mean transitioning a product that has been inhaled into the lungs and is a life-saving medication is clearly a much more serious business than replacing the propellant in a refrigerator or in hairspray, right, or in a car air conditioning system. You know, these are some of the other uses for these propellants that we are using. So yeah, it it’s a complex transition to make. It’s not just to drop in, we have thousands of hours of work, thousands upon thousands of data points of data to generate to be able to put the Joss together to then be able to show to the regulatory authorities and to be clear ourselves, that what we are proposing in terms of a formulation with a new propellant in it is safe, is effective, and is going to be safe in the patient’s hands. 

Louise Righton (26:55): 

And the patient really must be at the forefront of all of this, which is why none of us want to rush this. We want to work as quickly as we can to decarbonize, but in a safe and controlled manner without disruptions to supply chain, without patients not being able to get access to the drugs that they depend upon. So yes, it’s complex work. It’s technical work. It’s time-consuming work and it requires deep expertise across not only chemistry, but material science and engineering as well. And I’m pleased to say that we’ve got a fantastic combination of the very experienced scientists at Kindeva that have already been through this. And we’ve got the best of the best young scientists coming through as well, that are developing the new science that we need to be able to understand how these new propellants are going to perform once they’re in  medical aerosols, in pMDIs. 

Louise Righton (27:56): 

So, and this transition is going to happen faster. So even though it’s just as complicated as the CFC to HFA transition in the early ‘90s, global warming says that this has got to happen quickly. We can’t wait. And so that’s why the industry’s working night and day really on this problem. And we have all that experience, not only in Kindeva, but across the industry as well, of course, we have that experience from the early ‘90s to build upon. And so if any of the listeners aren’t aware, as I think I mentioned earlier, the first products will be available and coming to the market by 2025. Four companies including Kindeva have announced their intention to have the first new green propellant containing pMDI to the market before the end of 2025. And that’s the rate of change now. Eerything speeds up, doesn’t it, John? But that’s the rate of transition now, and it’s going to be a lot faster than it was last time. 

John Price (28:57): 

Okay. Yeah. Being familiar with the industry four years seems really fast. So I mean, I know it’s faster than previous transition. To wrap up here, it seems like coming into this, I probably was under the opinion, like, why don’t we just change quick? And it sounds like it’s really important to take that patient-centered approach and kind of a broader view instead of just running and jumping off the cliff, thinking we’re doing the best thing, we really need to build a ramp. It’s going to take some time to get where we want to get, but taking that time is the only way to do it the right way. So I really appreciate your insight and the information and I know all the hard work you’ve done on this. So anything else you want to add before we sign off here? 

Louise Righton (29:41): 

John, I think you’ve hit the high points there and one of the things I always stress and as IPAC, our trade association, we always stress in our key messages as well, is that the patient is what is important here. And the patient must be at the forefront and the center of our thinking. And at the end of the day, we talk a lot about the chemistry, the science, the regulation, the environmental policy. And at the end of the day, we must remember that we are talking about putting a product in the patient’s hands that they rely upon, and which gives them a quality of life. And also in many cases saves their life as well because asthma and COPD are both acute life threatening conditions as well as being chronic conditions. So let’s all remember that keep working hard as an industry, we’ll certainly keep working hard as Kindea to lead the industry through this transition and look forward to seeing what the next four to five years brings in terms of new, more sustainable pMDIs to keep patients well. 

John Price (30:49): 

Thank you for listening to Coffee with Kindeva, series of thought-provoking conversations about complex drug delivery. Join us next time as we continue the journey into the fascinating world of Kindeva Drug Delivery.