13 - SUSTAINABILITY: Breath of fresh air

Chlorofluorocarbons (CFCs) first entered human use in the late 1920s and were popularised in the 1930s as ‘miracle refrigerants’.

CFCs found myriad uses, including as propellants for products from whipped cream to pressurised metered dose inhalers (pMDIs). By the 1980s, however, they were found to be contributing to a sizeable hole in Earth’s ozone layer. Adulation turned to vilification, and production of CFCs was essentially halted entirely in 2010 ‘nder the terms of the Montreal Protocol.

Meanwhile, CFC propellants in pMDIs have been largely replaced with hydrofluorocarbons (HFCs). HFCs break down in the atmosphere more rapidly than CFCs and so have a significantly lower propensity to deplete ozone. Nevertheless, many HFCs are potent greenhouse gases, owing to strong absorption of infra-red radiation. Research published by NASA in 2015 found that the impact of HFCs was likely to be around 100 times greater than previously estimated. HFC-134a – which is frequently used in modern pMDIs – has a global warming potential (GWP) about 1,300 times greater than carbon dioxide.

HFCs in pMDIs are thought to account for only around 2.3% of emissions from fluorinated gases and as little as 0.03% of total greenhouse gas emissions. Nevertheless, the use of pMDIs can be a substantial contributor to the total carbon footprint of pharma companies working on respiratory illnesses. For example, GSK estimates that patient use of its pMDIs accounts for around 45% of its entire carbon footprint, while prevalence of respiratory illness is likely to drive up future demand for inhaled therapies.

One proposed solution is to swap pMDIs for alternative inhaled drug delivery systems, like dry powder inhalers (DPIs), which remove the need for a propellant altogether. Chiesi Farmaceutici and GSK estimate their DPIs have a carbon footprint about 12 to 24 times lower than pMDIs. This approach, however, is not a catch-all as there remains a clinical need for pMDIs, particularly for patients with low inspiratory flow. Replacing propellants with greener alternatives across pharma is a vital route to explore.

Chiesi is currently investigating low GWP propellants in collaboration with Koura and GSK also has a low carbon propellant at preclinical stage. Both GSK’s and Koura’s propellants are purported to offer a ~90% reduction in inhaler carbon footprint.

Future pMDIs using these propellants could have a similar environmental impact to equivalent DPIs, meaning treatment choice can be driven by clinical rather than environmental considerations.

Recently, AstraZeneca announced positive results from a first-in-human phase I trial of a propellant (HFO-1234ze), developed in partnership with US conglomerate Honeywell, which has ‘near-zero’ GWP. AstraZeneca wants its product – Breztri – to be first on the new pMDI platform. Indeed, the company’s sustainability report reveals ambitions to put these next generation pMDIs on the market by 2025.

With several projects on the cusp of market deployment, this hot area for inhaled drugs will hopefully contribute to a cooler future for pharma and the planet.