The route to regulatory approval for a new product can seem complex, and even more so when the process itself is evolving. The pressurised Metered Dose Inhaler (pMDI) industry is familiar with change, having been through a significant shift from chlorofluorocarbon (CFC) to hydrofluoroalkane (HFA) propellants in the past 30 years. Now it is in the midst of another transition that is moving much more rapidly, requiring coordinated efforts across the entire value chain to bring low carbon pMDIs to market. With Pharma, CDMOs and other supply chain partners collaborating to refine the technology needed, it is now key for regulations to be clear and well understood in order to accelerate approvals for the next generation of pMDIs.
Current state of the regulatory landscape
The Kigali Amendment to the Montreal Protocol is the international agreement driving the phaseout of high Global Warming Potential (GWP) HFAs across multiple industries, including Pharma. However, the pressure is highest on the industries that use the largest quantities of HFA propellants – namely, the refrigeration, air-conditioning and heat pumps (RACHP) sector. As current RACHP applications are switched over to the next generation of propellants, the supply chain for HFAs shrinks, availability decreases, and prices rise. As a result, the inhalation sector faces pressure to adopt alternatives before regulations necessarily dictate it. Whilst the first marketing authorisation has recently been granted by the MHRA in the UK, the regulatory process for new, low carbon pMDIs is not fully established or tested. This means we are now in a position in which many of the key players are updating their pMDI products with the next generation of propellants, but the route to approval is still evolving.
Different regulatory authorities are approaching this transition in different ways. For example, in the EU, the European Medicines Agency (EMA) has taken a proactive approach, bringing key stakeholders into the conversation to help shape regulations, whilst in the US, the Food and Drug Administration (FDA) have been more reactive, waiting to develop the process as it is needed. A key reason for the regulatory uncertainty around switching to the next generation of propellants is the fact that the propellant makes up 95% of the formulation, despite only being one component. In addition, the properties of the chosen propellant might require changes to other aspects of the device, such as materials used in the metering valve. As a result, there isn’t a one-size-fits-all pathway to regulatory approval.
Bringing the industry into the conversation
With the regulatory landscape in a time of transition, now is the time for the industry to input and help to shape the process. Regulatory bodies are taking cues from early adopters of alternative propellants, but there is an opportunity for all stakeholders to work collaboratively together to help guide the conversation around necessary regulatory updates. Until late 2024, much of the discussion between industry and regulators had been led by the EMA. However, a workshop led by the FDA in October 2024 made significant progress in opening up the conversation. This workshop created a new space for stakeholders to ask questions, highlight challenges and work together to bring about solutions –– and it appears to have had an impact. In more recent industry interactions, the FDA has signalled a willingness to move towards a position whereby it will more closely align with the EMA’s approach and data requirements. We have yet to see a formal position; however, signs are promising that the direction of travel is towards an accelerated transition to the next generation of inhalers.
A leading voice
CDMOs have a particularly important role to play in key conversations because the number of different projects they work on gives them a significant level of interaction with regulators. At Bespak, we see it as an extremely important responsibility to be proactive in this arena. We are in a position to share insights from the perspective of product and process development, component selection and manufacturing with regulators, and to communicate the regulatory insight we develop with our customers. In this way, we can also add weight to the voices of the industry, to help drive regulations that align with the needs of developers, manufacturers, prescribers and patients.
To do this, we maintain a strong presence in industry-wide regulatory discussions and workshops, and also play a role in several industry groups. Bespak has been a member of the International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC-RS) for several years, and we are proud to be represented by members of the Bespak team on the board. IPAC-RS plays a vital role in advancing regulatory science and in disseminating its research and insights to the industry. Our membership allows us to contribute to this, ultimately helping to shape the pathways to regulatory approvals for low carbon pMDIs. We are also members of The Organisation for Professionals in Regulatory Affairs (TOPRA), Regulatory Affairs Professionals Society (RAPS) and British Standards Institute (BSI) and attend conferences and webinars with these professional bodies. This helps us to keep up our own regulatory excellence. As a result, Bespak can act as a trusted voice as regulators consider their approaches.
Supporting our customers
In addition to our role in helping to shape regulation, we also are well positioned to support our customers with their regulatory strategies and processes. Bespak has significant regulatory expertise and decades of knowledge within its regulatory and compliance team, which we leverage throughout our customers’ projects. In addition, we bring in our internal subject matter experts with experience across quality, product development and product engineering for a more thorough, expertly informed approach to the regulatory process. This means that customers can rely on our support in scientific advice meetings, for authoring appropriate sections of the regulatory submission, and in helping to make a case to regulators. Beyond this, we are committed to sharing our knowledge with the industry –– for example, through our blogs and newsletters or by leading workshops and podium sessions at scientific conferences.
We believe that collaborating and sharing knowledge is the best way to fuel progress in the industry, and we employ this approach across all of our technology platforms. Our mission is to help millions breathe more easily, and enabling the transition to the next generation of low carbon pMDIs is a key part of that.
Speak to us to be part of the conversation and discover how we can support you through the green transition.
