Nick Atkinson, Head of Project Management - Drug Product Development
Leading the green propellant transition: a formula for success
Adopting a greener approach
The timeline for the phasedown of fluorinated greenhouse gases, originally agreed as a result of The Kigali Amendment to the Montreal Protocol, looks likely to be accelerated from its original timescales. Updates to regional legislation, such as the recent review of EU F-gas Regulation, is expected to result in earlier phasedown targets and an eventual phaseout, certainly in several key regions.
Such regulation applies to the current hydrofluoroalkane (HFA) propellants used for pressurised metered dose inhalers (pMDIs). Developing and manufacturing pMDIs with alternative low global warming potential (GWP) propellants is therefore an urgent industry priority to maintain the supply of life-saving medicines for patients, and ensure business continuity for pharmaceutical companies.
Enabling this transition to low GWP propellants is something that we at Bespak have been working on since 2020, and is something our team is really passionate about. This work means that we are able to continue producing vital asthma and COPD treatments in the pMDI format that patients are familiar with, whilst also reducing their impact on the planet.
There are a lot of complexities to this transition that we must consider, spanning formulation and product development, regulatory considerations, component design and manufacturing, and production engineering. Collaborating with experts in the industry, we have been pioneering solutions and best practices to help inform and drive the adoption of low GWP propellants in pMDIs. From our work so far, we have demonstrated the feasibility of developing formulations with both new propellants: HFA-152a and HFO-1234ze. Our expert teams continue to study the effect of the propellants on shelf life, aerosolisation and valve performance, as well as how this impacts device design, helping us optimise our approach. We recognise our responsibility as a leader in this transition, and it is fantastic to see the results of all of our work so far, as the first CDMO to manufacture at commercial scale using HFO-1234ze.
Expanding to meet growing demand
An exciting milestone in our work to support the green propellant transition is the installation of our new high-speed commercial filling equipment for greener pMDIs at our Holmes Chapel, UK, site. This is a key step in preparing for evolving demands from our customers. Currently, low carbon pMDI manufacturing capability in the industry is limited and, as the transition gains pace, demand for capacity will continue to grow. Businesses are therefore looking to secure their manufacturing capacity for the coming years.
In anticipation of this demand, and supporting our vision to be the industry’s sustainability leader, we have invested in expanding our capacity with two new filling lines, and have further expansions planned. Our latest line, which is currently being manufactured, is capable of filling pMDIs with both of the new low GWP propellants, and will be producing commercial batches by Q4 2027. Our early experience as a first-mover, combined with our deep expertise in adapting to and handling the new propellants, means we are now ideally positioned to support customers with pMDI development and manufacture—whether they choose HFA-152a or HFO-1234ze—as the industry continues to evolve into the future.
Collaborating to pave the way
We have always found that collaboration is the key to success, and through our strategic partnerships we are in a strong position to lead the transition to low GWP propellants. For example, through our collaboration with Solstice, we have developed a deep understanding of the properties of HFO-1234ze. This allowed us to adapt our filling lines to work with the propellant with minimal changes, helping us produce the first commercial batches using HFO-1234ze—a first for the CDMO industry.
Similarly, we are looking to lead the industry on the adoption of HFA-152a. We are working with the supplier—Orbia—to strengthen our understanding of the propellant, and with the manufacturer of our filling lines—DH Industries—to optimise our filling process. Based on this work so far, we have developed the Zephex® 152a Safe Handling Guide for pMDI Manufacturers, a vital resource to support the industry, and to guide us as we prepare for commercial-scale manufacturing with HFA-152a. Our goal is for as many pMDI products as possible to transition to the new low GWP propellants, whether we manufacture them at Bespak or not. With that aim in mind, we continue to collaborate to share our knowledge and experience as the industry works to navigate the change.
Addressing safety challenges
HFA-152a is a flammable propellant, which brings about additional challenges beyond just adapting production for a new formulation. Through our close collaboration with the suppliers of both the propellant and the manufacturing equipment, and the in-depth understanding this has enabled, we have developed comprehensive process safety studies and a safe handling guide for our industry. We have also taken learnings from other industries on how they are using these materials in their processes; for example, most consumer aerosols such as deodorants or spray paints use flammable propellants. We can apply knowledge and best practices from these industries to our own manufacturing processes to maximise safety, adhering to guidance written by the British Aerosol Manufacturers’ Association, known as the BAMA Guide.
Bringing together our expertise in the development and manufacture of pMDIs with our track record of embracing and driving change in the industry, we are proud to be playing a pivotal role in the low GWP transition. We look forward to working with more customers to bring low carbon pMDIs to the patients that rely on them.
