Paul Hardman, managing consultant, Broughton, explores the current situation and ways of reducing greenhouse gases in this sector.
Broughton
Pressurised metered-dose inhalers (pMDIs) are essential for treating respiratory conditions like asthma and COPD, but their hydrofluorocarbon (HFC) propellants are potent greenhouse gases that contribute to global warming. As environmental concerns grow, reducing these emissions has become a priority in healthcare. The pharmaceutical industry can address these challenges by investing in research for low-global warming potential (low-GWP) propellants.
The NHS Long Term Plan aims to cut emissions by increasing the use of lower-carbon alternatives like dry powder inhalers (DPIs), greener disposal of used inhalers, and supporting innovations in lower-carbon propellants. As pMDIs make up 70% of the inhalers prescribed in the UK, a 30% shift to DPIs could reduce emissions by 374 kilotons of CO₂ equivalent (ktCO2e) annually.
The current propellants
Previous efforts to make inhalers environmentally friendly followed the Montreal Protocol, which phased out chlorofluorocarbons (CFCs) due to their ozone depletion effects. HFCs were adopted as a more ozone-friendly alternative. However, a major drawback is their GWP is much higher than that of carbon dioxide (CO₂).
These gases can persist for extended periods in the upper atmosphere, permitting solar radiation to enter while trapping reflected emissions and re-radiating energy back toward the Earth. In response, global regulatory efforts, such as the Kigali Amendment, are now focusing on the phasing out HFCs, particularly in medical applications, to mitigate their impact on the environment.
The path to greener inhalers
Another established product on the market is the DPI. DPIs deliver medication to the lungs in dry powder form, with the medicine stored in individual blisters. Each blister contains a precise amount of the powdered medication, typically a single dose.
DPIs have the distinct environmental advantage of containing no propellants and, therefore, no HFCs. DPIs rely on the patient’s inhalation effort to deliver medication. When the patient inhales through the device, the air flow disperses the powdered medication, carrying it into the lungs. This eliminates the need for propellants like HFCs, making DPIs a more environmentally friendly option.
However, some patients – typically the very ill, elderly or very young – will be unable to generate sufficient inspiratory flow to correctly use a DPI, in which case only a propellant-driven pMDI will suffice.
Low-GWP propellants
Recent advancements have led to the development of low-GWP propellants, such as HFC 152a and HFO 1234ze(E). These alternatives significantly reduce environmental impact compared to traditional propellants. Companies like AstraZeneca and Chiesi are actively working to bring these new propellants to market, with expected launches by 2025, marking a significant step towards more sustainable inhaler options.
HFO 1234ze(E) is the most probable replacement option due to its low GWP and its similar physical characteristics, including density, vapour pressure, and dipole moment, with commonly used propellants like HFC 134a. This can also help simplify the transition process in inhaler design.
The industry’s role in the transition
The introduction of new propellants is subject to strict regulatory scrutiny. Manufacturers must undertake a series of evaluations to ensure safety and effectiveness. Evaluations for extractables and leachables are necessary to ensure new propellents do not result in extracted compounds of toxicological concern from the container closure system that may leach into the medication over the shelf life of the product.
The U.S. FDA's Guidance for Industry sets regulatory expectations for propellant-based inhalers, requiring thorough toxicological assessments and ensuring new formulations meet safety, effectiveness, and patient use standards.
Similarly, the EMA’s Guideline on the Pharmaceutical Quality of Inhalation and Nasal Products mandates rigorous evaluation of any changes in propellants or components, along with studies on drug delivery performance and device compatibility.
Gaining regulatory approval for new propellants can be a lengthy process due to various challenges. By investing in research and development for low-GWP propellants, companies can lead the charge in creating environmentally friendly alternatives.
Collaborating with specialist firms can accelerate this process, ensuring that new technologies are developed and brought to market more efficiently. However, while it's essential to focus on reducing environmental impact, it is equally important to maintain a patient-centred approach.