Breathe it in: The environmental concerns of inhalers
Pressurised metered dose inhalers (pMDIs) are essential medical devices for patients with asthma and COPD, but there is growing concern about the carbon footprint these treatments place on the environment. Dr David Lewis, director of Aerosol Research, Chiesi, assesses the situation.
Pressurised metered dose inhalers (pMDIs) have long been the major treatment of choice for treating asthma and chronic obstructive pulmonary disease (COPD), but the effect of pMDI propellants on the environment is the subject of ongoing governmental and industrial debate. The ban of chlorofluorocarbons (CFCs) in 1996 due to the substance’s role in the depletion of the ozone layer led to the redesign of pMDIs and the development of hydrofluoroalkane (HFA) as a new propellant. Now, however, there is building evidence that HFAs, namely the widely-used HFA-134a, have high global warming potential, and are being targeted for regulatory reform.
There is an argument that dry powder inhalers (DPIs) may be a suitable replacement for pMDIs, due to their clinical equivalency, but the fact that not all patients are able to use DPIs and the cost implications make this a complex issue and one that needs careful review of the facts and evidence. Patient preference is another key factor in choosing the appropriate technology for treatment. Compliance with medication is an ongoing issue and if patient choice is removed, there is a risk that adherence to prescriptions could drop.
pMDIs and DPIs – what’s the difference?
The inhalation technology behind pMDIs and DPIs differ in a number of ways, including how the drug dose is delivered, the inhalation procedure, and the way the active pharmaceutical ingredient (API) is contained within the formulation. In a DPI, the API is formulated in a dry powder blend and, in contrast to pMDIs, requires energy from the patient’s inhalation maneuverer to draw a pre-metered dose into the lung. MDI formulations contain a propellant, the most common being HFA-134a and HFA-227ea, which provides the energy needed to atomise the formulation and deliver the API.
The advantage of using a DPI is that drug delivery is automatically coordinated with the patient breathing in, whereas the actuation of a pMDI (not fitted with a breath actuation mechanism) must be coordinated with inhalation – an action which some patient groups find challenging. Breath actuated mechanisms are available for pMDIs, but they are not required by regulation. However, a major disadvantage of DPIs is that they require the patient to breathe deeply and forcefully to effectively deliver the dose. Different patient groups, such as geriatrics and paediatrics and those with significantly compromised lung function (for example COPD, lung cancer and emphysema patients) have variable breathing profiles, potentially resulting in limited aerosolisation of the formulation and therefore compromising effective drug delivery.
Cost implications of different devices
It is important for the government to consider the cost implications when assessing the regulations behind HFA use. Determining the relative costs of pMDIs and DPIs depends on a number of factors, such as device complexity, formulation, and number of doses per device. For example, pMDIs are cheaper devices, and provide between 100-200 doses per device, whereas DPIs have approximately 30-60 doses. Therefore, the approximate price per dose of DPIs is 40% higher than pMDIs [1]. If, due to their effect on the environment, the removal of pMDIs was mandated in regulation, the cost implications for the NHS could be significant.
Innovate around regulation
pMDIs and DPIs are both associated with relative environmental impacts, and the emissions are attributed to different stages of each device’s life cycle. For example, a Product Carbon Footprint Certification Summary Report conducted by the Carbon Trust on behalf of GlaxoSmithKline (GSK) [2], showed that the majority CO2 emissions from DPIs are derived from the production of the plastic device and the APIs Fluticasone Propionate (FP) and Salmeterol Xinafoate (SX). The primary contributing factors of pMDI emissions are from actual use, and end of life when the product is disposed of.
The position of companies such as GSK, as well as the government, is to try to reduce the UK’s dependency on pMDIs. However, some companies are looking for ways to reduce the global warming potential of pMDIs, whilst still ensuring this treatment is available to the patient groups that rely upon it. For example, Mexichem is a company that develops propellants for pMDIs, and is at the forefront of innovation. In order to meet the requirements of pharmaceutical and environmental regulation, Mexichem is investigating the medical potential of 1,1-difluoroethane (HFA-152a), a propellant already used in consumer aerosols. The company claims that by making the switch, the carbon footprint of pMDIs could be reduced to similar to that of DPIs, which is 12 times lower than the emissions from HFA-134a [3] (figure 1). Initial studies have shown that HFA-152a has promising emitted dose efficiency and suspension stability, and the propellant could even enhance the stability of certain APIs [4].
It is important to consider the option of developing new formulations to overcome regulatory challenges, rather than disregarding a treatment altogether. A lack of scientific understanding within governmental bodies could restrict the innovative solutions that companies such as Mexichem are exploring.
Moving forward with MDIs
The need to reconsider the propellants used in pMDIs is evident. As with the phasing out of CFCs, the regulatory pressure for the phase-down of HFAs has already begun with some force. However, it has been recognised that it is not yet economically or technically reasonable to entirely replace HFA-propelled pMDIs. The design of both pMDIs and DPIs should be the subject of ongoing innovation and, although a new takeover technology can take a number of years to refine, the industry should be investing in the development of the latest, most sustainable solution at pace.
References
Minister questioned on UK progress on reducing F-Gas emissions, Environmental Audit Committee, 12th December 2017 https://www.parliament.uk/business/committees/committees-a-z/commons-select/environmental-audit-committee/news-parliament-2017/f-gas-evidence3-17-19/
GlaxoSmithKline Product Carbon Footprint Certification Summary Report, Carbon Trust, 2014.
Jeswani, H. and Azapagic, A. (2017) Environmental Assessment of Metered Dose Inhaler Propellant: Potential for a Reduced Carbon Footprint Alternative, Respiratory Drug Delivery Europe Abstract.
Corr, S. and Noakes, T. (2017) Pressurised Metered Dose Inhaler Propellants: Going Forward, Respiratory Drug Delivery Europe Abstract.