Craig Sommerville, senior vice president of the Metered-Dose Inhaler Business Unit at Kindeva explores how a combined approach to pMDI development can help to reduce risks and streamline progression from concept to clinic and beyond.
Kindeva
Around the world, millions of people use pressurised metred dose inhalers (pMDI) to address respiratory conditions.
The rise of conditions such as asthma and chronic obstructive pulmonary disease (COPD) means that pMDIs are an increasingly vital device for global health. This is driving market growth, with the MDI market estimated to reach $18.4 billion by 2034.
However, the development of pMDIs is demanding, due to a changing regulatory landscape, and technical and commercial challenges. Companies must be able to adapt pMDIs to meet new environmental standards, while ensuring they do not compromise patient safety and efficacy.
When dealing with these challenges, separating into siloes is increasingly risky. Taking a combined approach to pMDI development - which considers formulation science, device engineering, and performance testing in parallel - can help companies navigate pitfalls and make more informed decisions.
The challenges of pMDI development
The therapeutic benefits of pMDIs are achieved through a fine-tuned synergy of formulation and device design. Any alteration to one element will have an effect on the other, so it is essential that they are developed synchronously to produce the highest-quality products.
Furthermore, pMDI development is undergoing a period of change. The Kigali Amendment to the Montreal Protocol mandates that companies move away from hydrofluorocarbons (HFCs) to next-generation propellants (NGPs) with a far lower global warming potential (GWP).
While this shift will be beneficial for the planet, it is prompting companies to re-evaluate how they develop products at all stages of the process. Failure to properly align teams at key points in formulation, device design and manufacturing can lead to delays, unexpected costs and regulatory issues. This can affect the overall cost and time to market, and even lead to difficult conversations about whether continuing to manufacture such products is feasible.
The changing regulatory environment
It is important to be aware of the changing regulatory environment, which differs between major markets. For example, while combination products are fully regulated by the Food and Drug Administration (FDA) in the US, combination products in the EU are subject to dual oversight, and require assessment by a notified body as well as the European Medicines Agency (EMA) to ensure that both components meet required standards.
The shift to NGPs is also proceeding at a different pace in different markets. While the EU’s F-Gas Regulation took effect in March 2024, the US is currently establishing a state-level framework for its transition through the American Innovation and Manufacturing (AIM) Act, while the UK is shaping its own F-Gas regulations following Brexit.
With all of these factors to consider, pharmaceutical companies are increasingly looking to partner with contract development and manufacturing organisations (CDMOs) who can offer a more integrated drug-device development approach from concept to commercial manufacturing. This can mitigate many of these risks, allowing teams to act strategically and identify issues earlier.
For example, working with an experienced CDMO to proactively manage supply continuity can help companies to develop products with greater confidence. Approaches such as holding a buffer of safety stock can smooth out the development process, and prevent costly delays.
There are also considerable benefits to partnering with a single CDMO with broad development and manufacturing capabilities. This gives companies the opportunity to access a range of expertise and experience under one roof, instead of switching between teams in different locations. Furthermore, these CDMOs have a more complete understanding of products as a whole, meaning that companies will receive invaluable insights into how to transition to new formulations and device designs, without affecting efficacy or safety.
However, truly integrated drug-device development takes even more factors into account. For instance, an excellent integrated CDMO partner will be able to provide facilities where new NGP candidates can be handled safely, and manufactured at scale. They will also be able to work closely with companies to help them anticipate evolving and emerging legislation, and develop strategies which ensure that the products they develop are well suited for key markets - both now and in years to come.
The need for strategic, integrated thinking
The move to NGP propellants is a welcome shift toward greener pMDIs and could also serve as a catalyst for greater innovation in respiratory medicine. Over the next few years, we will see a fundamental re-engineering of pMDIs, adopting more environmentally-friendly practices while maintaining and even improving standards of patient safety and efficacy. Responding to the opportunities of this era of innovation requires a strategic view, and - crucially - a willingness to collaborate and embrace integrated thinking throughout the development process.
This means considering a range of needs and challenges from the very start. Companies need a broad understanding of how the drug and device perform in tandem, so they can optimise all elements of the product simultaneously. They need to consider performance and safety requirements from the outset. They need to plan ahead to ensure they have the required supply of components and can mitigate fluctuations in price and availability. They also need access to manufacturing facilities that meet the correct safety protocols and can scale up to meet demand.
When it comes to regulation, they not only need to meet existing requirements in different markets, but also anticipate and perhaps shape the emerging standards of the future.
A strategy such as this cannot be achieved by working in siloes. Instead, innovative companies and experienced CDMOs must work together to pool expertise, research, knowledge and insights - and develop strategies which streamline processes and improve outcomes.
Working in a more integrated way is not simply about derisking the development process. It is an essential strategy for delivering a more sustainable future, and continuing to deliver effective, safe and convenient therapies.