Pharma's green shift: dry powder inhalers promise lower emissions

Experts disagree on whether DPIs or low emissions pMDIs are the way forward for effective, environmentally friendly inhalers. Credit: Orawan Pattarawimonchai / Shutterstock

In a bid to improve the pharma sector’s drive to cut down greenhouse emissions, several companies are advancing dry powder inhalers (DPIs) for respiratory conditions that are more eco-friendly than older, pressurised models. But experts are divided on whether they can effectively treat all vulnerable patients.

Efforts to supplant pressurised metered-dose inhalers (pMDIs) with DPIs, most recently by the European Network on Climate and Health Education (ENCHE), have gained steam in recent years.

Companies like AstraZeneca and GSK, which have high-revenue-generating inhalers for asthma and chronic obstructive pulmonary disorder (COPD) in their portfolios, have each committed to becoming net zero for emissions by 2045, and have publicly said that innovation in inhalers can be a route towards these goals.

AstraZeneca’s Symbicort inhaler accounts for most of its inhalation portfolio revenue, projected by GlobalData to generate a total $2.5bn in 2024. Meanwhile GSK’s lead inhalers include Trelegy Ellipta, projected to bring $3.3bn in 2024 sales, followed by Relvar/Breo Ellipta and Seretide/Advair

GlobalData is the patent company of Pharmaceutical Technology.

However, there remains a debate on whether these DPIs can be effective enough for patients, particularly for those with reduced inspiratory capacity.

On October 14, ENCHE announced its initiative to train 10,000 medical students in what it calls ‘green prescribing.’ ENCHE, a consortium of institutions led by the University of Glasgow, stated that over the next three years, it aims to help students manage healthcare in the context of climate change.

Students will be taught to treat conditions exacerbated by climate change and to push environmentally friendly therapies, including DPIs. Supported by the World Health Organization, AstraZeneca, GSK, and Novo Nordisk among others, the network seeks to offer education in constituent medical schools and to influence national curricula to follow suit.

Another supporter of this initiative is Dr. Christer Janson, professor of respiratory medicine and allergology at Uppsala University, Sweden, who has researched the potential environmental impact of switching to DPIs.

In a 2019 paper, Janson calculated that pMDIs produce a carbon footprint 20–30 times larger than that of DPIs. Although the volume of an inhaler’s propellant may be small, the hydrofluorocarbons (HFCs) that are often used in these inhalers can have greenhouse effects 1,400 times greater than carbon dioxide.

Janson likens dropping pMDIs for DPIs to a person becoming vegetarian or switching to an electric car.

In the same paper, he stated that 70% of inhalers sold in the UK in 2017 were pMDIs compared to 13% in his native Sweden; applying Swedish DPI use to the UK would result in an annual emissions reduction equivalent to 550,000 tonnes of CO₂. “It would reduce the carbon footprint of the NHS by about 3–4%,” he says, driving home the importance of such a change.

Reduced emissions on this scale are particularly relevant to the pharmaceutical industry. Not only is it a major contributor to climate change, being more emissions intensive than the automotive industry, but it is also notably vulnerable to its consequences. A volatile climate poses a serious threat to international supply chains, while vast water supplies are needed to support research and manufacturing.

Though widely hailed as the environmentally sound option, researchers, clinicians, and patients are not all united in their views on whether DPIs are as effective as pMDIs.  

For example, a 2023 head-to-head comparison of a pMDI against a DPI for beclomethasone dipropionate plus formoterol fumarate to treat asthma found that the two methods were comparably effective. However, a real-world 2017 database analysis of UK COPD patients found that for fluticasone/salmeterol therapy, more moderate to severe COPD exacerbations were seen at certain doses when a DPI was used than with a pMDI.

Nonetheless, some experts, like Dr. Roberto Dal Negro, researcher at the National Centre for Respiratory Pharmacoeconomics and Pharmacoepidemiology, Verona, Italy, support the ENCHE initiative and the potential of DPIs. In his opinion, claims that DPIs are inferior to pMDIs are “fake news.” He noted that much of the belief that DPIs fall short lies with anecdotal patient experience, but that this is clouded by a certain placebo effect. “With the pressurised device the patient perceives the inhalation, due to the inhalation of the cold propellant, but the effective inhalation is a different story.”

According to Janson, the answer is not so simple. While he agrees that DPIs and pMDIs can be equally effective in treating COPD and asthma in clinical studies, pMDIs are still preferred for young children and the elderly who may not be able to use a DPI. Additionally, a pMDI with a spacer is preferred to provide a sufficient dose in an emergency situation.

Janson says individual experience also plays a role. In Sweden, where DPIs are the predominant form of inhaler, patients have few problems using them, whereas in the UK, patients are unfamiliar with DPIs given their relative scarcity and so prefer pMDI options.

One reason for apparent differences in efficacy and patient preference could lie with the user rather than the device, according to Dr. Piyush Mehta, deputy manager at Cipla, Mumbai, India. According to Mehta, “effective inhalation therapy depends 10% on the medication and 90% on patients’ education.” However, he too recognizes pMDIs are preferable for some applications, namely asthma attacks, due to their ease of use and independence from patients’ inhalation effort.

In early pMDIs, chlorofluorocarbons (CFCs), which have since been found to cause drastic damage to the planet’s protective ozone layers, were used as propellants. These were later replaced with hydrofluoroalkanes (HFAs), which is the current standard for pMDIs.

A third generation of propellants like HFCs and hydrofluoroolefins (HFOs) may offer an alternative solution to DPIs. These compounds have a lower global warming potential than HFAs while still providing the propulsion lacking in DPIs, seemingly vital for patients who are unable to derive full therapeutic benefits from DPIs.

AstraZeneca, a leader in this space, is aiming to file for approval of an HFO-based version of its Breztri inhaler. The propellant is reported to have 99.9% less global warming potential than conventional formulations. GSK, leading the COPD market with its Trelegy Ellipta inhaler, is planning pivotal trials of Ventolin inhaler with an undisclosed low-emissions propellant.

However, experts are divided on these options. Mehta says these are “a promising alternative,” but Dal Negro says they are unlikely to supersede DPIs. 

It is not just big pharma, but companies like Parma, Italy-based Chiesi are also working on low-emission propellants. It is testing a new, low global warming potential HFA propellant—HFA-152a—in comparison to an older propellant in a Phase III trial (NCT06264674), which is expected to be completed in 2025. This is part of a wide commitment by the company to achieve net zero emissions by 2035, an initiative in which Chiesi UK has invested €350m ($375m).

The philosophy at Chiesi is “the greenest patient is the well-controlled patient”, says head of communications Yasmin Ghariani. Chiesi also has DPI candidates in its developmental portfolio, but Ghariani warns that a blanket DPI prescription and requiring therapy switches could potentially worsen patient wellbeing. This in turn could actually increase the carbon cost of treatment.

“We encourage prescribers to take a holistic approach to treating patients and not just a narrow device consideration,” says Harriet Lewis, senior director of public affairs at Chiesi UK. Ultimately, Lewis notes that prescribers’ decisions to offer low-emissions therapies should not overshadow choosing the best therapy for each patient.