Why should inhaled drug developers consider formulating or reformulating with HFA 152a?
It became very clear to us about 6 or 7 years ago that regulatory efforts to reduce global warming potential emissions in industrial applications would almost certainly impact the MDI market, whether that was by direct regulation or by impact on the supply chain. So to ensure a sustainable business we would have to deliver improvements on sustainable footprint for the MDI platform.
HFA 152a is available in large quantity, and it has about a 95% reduction in global warming impact compared to 134a; so if you could formulate in 152a, you could achieve a huge step change in the environmental footprint of the MDI. In fact when we looked at it, you could get down to the same carbon footprint as a DPI today.
Before we went public with 152a at DDL 2016, we did some initial testing with most of the active pharmaceutical ingredients used in MDIs, and I think pretty much universally we found they made good formulations. In most of the cases they made better, more stable formulations be they suspensions or solutions. As a result, we have high confidence that 152a can replace both 134a and 227 in MDI formulations.
And to date, everybody who has tried has been able to formulate successfully with 152a in all the studies we know about. Some companies are looking at their existing portfolio to convert formulations in order to deliver sustainability benefits, and some companies are looking at new chemical entities and deciding that they should formulate in 152a now to avoid having to reformulate later.
How soon will 152a MDIs be a reality?
A large portion of the industry is already looking at converting to 152a, and Chiesi has already announced publicly that they plan to have a 152a product by 2025. I can’t disclose which companies besides Chiesi are working on 152a formulations, but I would say between 50 and 70% of the big commercial formulations currently out there are being looked at to convert to 152a.
The vast majority of the clinical and tox testing of 152a as a gas is complete, which means we now start progressing the regulatory approval for its use in commercial MDIs. We completed the in-human exposure of 152a in Quarter 1 this year, and we’ve completed longer toxicity studies as well. We’d expect to complete the regulatory approval process for use of 152a in MDIs in the US and UK sometime in early 2022, and the process is going on with other bodies as well.
What is the current status of HFA 152a production?
In 2021, Zephex 152a transitioned from being an R&D project we’ve been working on for 6 or 7 years into a commercial product. Koura is now finishing construction of the first commercial pharmaceutical grade 152a manufacturing facility in Runcorn, UK, adjacent to our 134a facility, which will be able to make several hundred tonnes of pharmaceutical-grade 152a per year. That amount enables customers to do their product registration work with confidence, and it will be enough quantity for initial commercial launches of product through about 2025 or 2026.
We are also making plans to add further capability in 2024-2025 and beyond. We expect more of the industry to make the change to 152a from 2025-2030; and when the market gets to maturity, we’ll be needing to make somewhere between 5,000 and 10,000 tonnes per year.
