Limiting the impact respiratory disease treatments have on the environment
Our most recent blogpost is linked closely with the content of a recent BBC News article by James Gallagher which highlights Why switching asthma inhaler could be better for you and the planet. As part of an NHS drive to address climate change, the BBC article reports the numerous and broad ranging advantages of switching from propellant-based inhaler devices to dry powder inhaler (DPI) systems. Not only will this allow for reduced environmental impacts of development, use and disposal, but DPIs can also facilitate better control of symptoms in patients. This philosophy is firmly echoed by CrystecPharma where one of our core areas of focus is on generating better respiratory products for patients, affordably and in greatly accelerated timeframes. This is enabled because of the unique ability that the Crystec mSAS® platform has in the controlled precipitation of particles that have been engineered for ease of aerosolisation and optimised lung delivery.
This article summarises the latest research into the environmental impact of treating respiratory disease, the commitment of the NHS minimise their contribution to climate change, and how Crystec are enabling the accelerated development of greener, more effective treatments globally.
The environmental impact of treating respiratory diseases
A major challenge of modern life is the recognition of our actions on the global environment, and identifying means by which to reduce, eliminate and reverse this. The environmental impact of the healthcare industry, particularly in the management of respiratory disease, is a complex issue. Global warming and air pollution are directly linked to increased prevalence of respiratory diseases (such as COPD and Asthma), as well as increased exacerbations (a worsening or flare up of symptoms) for such conditions. In many cases, however, the treatment options themselves can contribute to air pollution and global warming.
As with the manufacture of any product, inhaler devices used to treat respiratory conditions have an inherent environmental cost across their life-cycle. Production of both the drug substance and the drug delivery devices require the use of solvents and raw materials, as well as energy inputs, which can all impact the environment. Additionally, the devices themselves are produced using plastics, meaning that careful disposal is also important. Furthermore, the extensive use of pMDIs (pressurised Metered Dose Inhalers), which contain hydrofluorocarbon propellants, can have a significant environmental impact. It is therefore increasingly important that approaches to preventing and treating respiratory diseases include careful consideration of their broader context and implications.
The responsibility for addressing this paradox sits with everyone from governments to individuals, including healthcare providers, pharmaceutical companies and patients. Above all, patient care cannot be compromised, and it is vital that effective, easy to use treatments exist, and continue to be improved, in order to prevent exacerbations, which in addition to damaging health, carry their own environmental burden. Whilst Asthma patients, for example, may have more at stake than most on ensuring proactive management of climate change, their influence must be translated into regulatory action. Ultimately, providing patients with a choice of treatment options that allows them to effectively manage their condition, while simultaneously enabling a responsible and pragmatic approach to climate change is of paramount importance to the pharmaceutical and healthcare industries globally.
Greener NHS Campaign
At the start of 2020, the NHS announced a commitment to a Greener NHS campaign to tackle a ‘climate health emergency’. Noting that air pollution and climate change contribute to 10s of thousands of UK deaths annually from conditions such as heart disease, stroke and lung cancer, the campaign has been developed to reduce the carbon footprint of the health and care system in England, which is currently responsible for an estimated 4-5% of England’s carbon footprint. A major part of this strategy is to transition (where clinically appropriate) from Metered Dose Inhalers, MDIs (which typically use fluorinated gas as a propellant) to Dry Powder Inhalers, (DPIs). It is anticipated that a shift to lower carbon inhalers will not only deliver a reduction of 4% reduction in the carbon footprint of the NHS, but an open article published by the British Medical Journal found that that considerable cost savings can also be achieved. The report touched on a range contributing factors, including waste, ease of use and patient adherence, which suggested advantages to DPI use across the board, and even supporting improvement in patient technique.
DPI vs low GWP propellants
An alternative approach to reducing the environmental impact of inhaler devices, and one that has been championed by Chiesi, is to reformulate MDIs with low Global Warming Potential (GWP) propellants. However, these new propellants remain at the early stages of development and must go through extensive clinical testing prior to approval for use in patients. As such, the use of simple, economical and eco-friendly DPIs, some of which have demonstrated a carbon footprint 18 times lower than a pressurised MDI, remain a highly attractive option.
Crystec’s mSAS® technology – a greener way to facilitate the development of more environmentally benign respiratory therapeutics in greatly reduced timescales
There are currently several crucial barriers which prevent, and slow down, the development of effective DPI products using conventional approaches. This ultimately drives the use of propellants in the pharmaceutical industry, as mentioned above. The key factors which influence the performance of a DPI product include the Emitted Dose, ED (the amount of a drug/formulation which leaves the inhaler/device), the Fine Particle Fraction, FPF (the percentage of drug which reaches and stays in the lung), and the bioavailability (the proportion of drug which reaches the bloodstream and has a medicinal effect). Each of these is directly reliant on the properties of the drug particles themselves (e.g. particle size), which are greatly influenced by the method of their manufacture.
Conventional techniques typically used to manufacture inhaled products (that can achieve the necessary particle size requirements - typically 1 - 5 µm to ensure optimal lung deposition), often result in powders with unfavourable physical qualities such as static, instability and non-uniformity. In addition, these processes (e.g. spray drying, milling) generally involve multiple steps which increases process inefficiencies, costs and introduces complexities post manufacturing that have to be worked around to facilitate adequate product performance for patients (e.g. drug formulation and device development). These issues can all potentially impact on the environment through increased raw material and energy usage, as well as lengthening the time needed in development before the product can reach patients in need.
Crystec’s mSAS® (modified Supercritical Anti-Solvent) technology is an attractive alternative to these conventional approaches, using supercritical carbon dioxide as an anti-solvent to precipitate particles with precise control. mSAS® is a single step, bottom-up process, which is uniquely suited to the rapid generation of optimised particles for DPI delivery. The platform enables particles to be precipitated directly from solution with a high degree of control over their particle size, as well as a range of crucial parameters such as particle shape, solid-state form and composition. In addition, the particles have extremely smooth surfaces and low levels of electrostatic charge meaning that they do not stick together. These features combined mean that mSAS® particles can be easily aerosolised, achieving very high levels of lung deposition even from simple, inexpensive and readily available DPI devices. In addition, this means that even in patients with compromised respiratory function, the drug delivery will still be highly efficient.
In addition, when compared directly to conventional drug development and particle size reduction techniques, which often include multiple process steps (e.g. crystallisation, milling, spray drying), mSAS® can offer a simple, faster, and greener alternative. Conventional technologies typically involve the extensive use of organic solvents, considerable heating/cooling requirements and long cycle times. Conversely, mSAS® can be operated at close to ambient temperatures, requires minimal use of organic solvents, has few moving parts (contributing to lower energy requirements), and involves a single manufacturing step which typically occurs within a few hours. Although carbon dioxide is a core component of the process, it can be harvested and recycled as a by-product of existing processes (e.g. brewing), and then reused in the generation of pharmaceutical products. The mSAS® process is therefore is not contributing to CO2 release, but rather using CO2 that would already be generated.
Overall, the precision and efficiency afforded by the mSAS® platform facilitates the development of strongly performing DPI therapeutics capable of being delivered from inexpensive inhaler devices, that would otherwise require the use of a propellant to facilitate lung delivery. Ultimately enabling the accelerated development of cleaner, greener, more effective and more affordable treatments for respiratory disease.
For more information about how Crystec can reduce the environmental burden of your respiratory programmes and streamline your development, please get in touch today. Our Business Development Director, Catherine Hunter, is eager to explore how we can support you.