Picking up speed: The propellant transition accelerates
The Kigali Amendment to the Montreal Protocol is a key piece of legislation that has been shaping the future of the pressurised Metered Dose Inhaler (pMDI) industry. The Amendment was agreed by the United Nations (UN) countries in 2016, with an aim to phase down global hydrofluoroalkane (HFA) consumption by 80–85% by 2047. However, regions and regulators are introducing their own interpretations, which may drive a faster transition than is mandated by the agreement.
Tightening regional regulations
Various regions are bringing in more restrictive regulations that go beyond the original aims of the Kigali amendment. For example, the new EU regulation removes the current exemption for pharmaceutical use, and states use of fluorinated gases (F-gases) for pMDIs will be limited via quotas to meet the EU Green Deal goal to make Europe the first climate-neutral continent in the world. Such legislation could result in a complete phaseout by 2050. In addition, the EU is taking significant steps to regulate PFAS (per- and polyfluoroalkyl substances) under the REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) regulation, which could see a ban on current propellants as early as 2027.
Propellant economics and availability
HFA-227 and HFA-134a are the two propellants currently used in pMDIs, and more broadly across different industries, whose carbon footprints are an increasing cause for concern. Whilst evolving regulations will ultimately enforce a transition to low Global Warming Potential (GWP) options in pMDIs, market forces add to the pressure. Reduced availability of current propellants across other industries, due to their own sector-specific regulations, increases costs. With HFA propellant quotas for medical use now pooled with those for industrial use, the combination of quotas and reduced manufacturing volume will continue to drive up the price of currently used propellants.
Carbon tax on quotas, plus individual countries considering national taxation will add to this cost burden.
HFA-227 has already significantly increased in cost, and HFA-134a is also starting to show some price increases. This is because, currently, industrial-grade HFA-134a enables lower prices for medical-grade material. As the allowable volume of industrial-grade propellant is reduced, the cost of medical-grade propellant will increase.
The race to the first low carbon pMDIs
Health systems, such as the National Health Service (NHS) in the UK, have ambitious net zero targets to meet, and pMDIs are a source of emissions that, whilst small, are viewed as a near-term target for reduction. As a result, alternative inhaler technology is being considered. So far, the approach has been to promote a switch to Dry Powder Inhalers (DPIs), which don’t require propellants at all. However, switching patients to an unfamiliar delivery device that may not be suited to them can impact the efficacy of the treatment and control of symptoms. This could ultimately result in exacerbations and hospitalisations, which have a far greater impact on the carbon footprint and overall cost of patient treatment than the choice of inhaler.
It is therefore important that the industry and healthcare providers have the option to prescribe the treatment best suited to individual patients, creating a need for low carbon pMDIs. Low GWP alternative propellants HFA-152a and HFO-1234ze have proven feasibility in pMDIs, and are the current focus for transition.
Shaping the new market landscape
With an increasing demand for low GWP pMDIs, a whole new market opens. The CFC-HFA transition taught us that no company is assured of maintaining their market presence – some products will fail or be voluntarily withdrawn, and new ones will enter and prosper.
However, the dynamics are different this time. Rather than a ban, this is a phasedown under the Kigali amendment (although some regions require an ultimate phaseout), which creates uncertainty around the economics of propellant manufacturing and supply. It is likely that supply chains and the costs associated with supply will be impacted more quickly than regulations, and will be the key driver of the speed of the global transition.
Pharmaceutical companies are therefore already facing pressure to accelerate their transition plans. We are seeing the beginnings of a ‘land-grab’, in which those who secure manufacturing capacity first will enter the market and gain market share, whilst those who aren’t ready will lose out. Early movers who have committed to decarbonising their pMDI portfolios are likely to be rewarded with favourable prescribing and reimbursement conditions, allowing them to increase their market share. The paradigm shift cannot be under-estimated – incumbents will have no protection from the accelerating market dynamics, and new entrants will seize opportunities.
Preparing for the transition
Pharma is weighing up the cost of change – and how to intelligently navigate this transition. Net zero commitments have been made, but now it is time to take steps to execute them. For example, the new propellants will need new manufacturing equipment and significant investment will be required. This is particularly true for the low GWP propellant HFA-152a, which requires mitigation measures in handling due to its flammability.
There is also intrinsic ‘cost to change’ that is required, covering product reformulation, data generation, clinical trials and the cost of the new propellants themselves. Plotting a path to market is therefore vital – and a key decision is whether to manufacture in house or to outsource.
Navigating the change with Bespak
At Bespak, we recognise our role in enabling the transition to low carbon propellants. We have made early investments in our capabilities so that pMDI developers can leverage our expertise, facilities and capacity to support their low GWP transition.
We have confirmed that all current APIs and commercial formulations can be reformulated and are technically feasible in low GWP with either HFA-152a or HFO-1234ze. In addition, we have validated our trusted valves across the full range of low GWP pMDI formulations.
We have not only manufactured at commercial scale with HFO-1234ze and installed a new high speed filling line to meet customer demand, but we have also committed to a further two pMDI production lines for delivery in 2026. These lines are specified to manufacture with both new propellants, reflecting our commitment to meeting the growing demand for low GWP pMDIs. Bespak is already able to fill at development and pilot-scale (in a GMP environment suitable for clinical supply) with both of the new propellants. As a result of these recent investments, Bespak now has the capability to develop from lab to pilot-scale and to scale-up into commercial production for all low GWP formulations, with both HFA-152a and HFO-1234ze.
Bespak can support any strategic option to help customers with low GWP pMDI development and commercialisation, whether that is transition arrangements to support temporary production or long-term outsourcing as an exclusive or second source of supply.
Get in touch to discover how Bespak’s specialist inhalation capabilities can help you get ahead in the transition to greener pMDIs
