TheraPHIX™
Developing a thermostable solution to transport RNA vaccines
The challenge
The COVID-19 pandemic accelerated RNA vaccine technology, saving millions of lives around the world.
Despite this unprecedented success, it also revealed a specific and significant challenge. RNA is susceptible to degradation by heat, enzymes and physical force, so long-term storage and transportation often requires freezing temperatures as low as ‑50°C. This is far colder than the 4°C or ‑20°C “cold chains” used for conventional vaccines. That makes getting effective RNA-based vaccines to all corners of the globe more costly, energy-intensive and practically impossible at scale.
CPI worked with RNAssist to develop a thermostable formulation to store RNA vaccines encapsulated in lipid nanoparticles (LNPs) without needing a freezer. This was achieved using deep eutectic solvents (DES), non-aqueous, non-organic solid solvents that form a compound liquid when mixed. With funding from Innovate UK, we were able to provide state-of-the-art facilities and formulation expertise at our National Formulation Centre and National Biologics Manufacturing Centre.
We developed two workflows: one that encapsulates DES within the RNA-LNPs (internal DES), and another where the DES is added after the RNA vaccine-LNP complex had already been formed (external DES). The resulting TheraPHIX™ formulations will enable manufacturers to store RNA vaccines at ambient temperatures, with the potential to revolutionise vaccination campaigns and improve global vaccine equity.
“With CPI, we’ve shown that ambient-stable vaccine formulations are achievable, enabling global vaccine equity. CPI’s expertise, including proving the large-scale manufacturability of our TheraPHIX™ stabiliser, has advanced us far faster than we could have managed alone, giving us the credibility to aim for widespread adoption by vaccine manufacturers worldwide.””
How CPI helped
- Provided specialised expertise in nanomedicine process development.
- Provided state-of-the-art formulation equipment for efficient mixing and purification.
- Optimised encapsulation conditions for each internal DES LNP.
- Scaled up production of internal DES RNA-LNPs six-fold.
- Optimised analytical methods for each DES LNP, including physicochemical characterisation and biological performance testing in cells.
- Performed comprehensive stability assessments for DES LNPs including accelerated ageing conditions and long-term stability.
Achievements
- Developed two workflows, one internal DES and another external DES.
- Successfully established encapsulation processes for each internal DES RNA-LNP.
- Successfully assessed stabilisation effect of DES as external excipients in different conditions.
- Demonstrated that external DES LNPs maintained RNA purity after a 3‑month storage at 37°C.
- Initial potency testing shows that internal DES RNA-LNPs exhibited higher activity than control LNPs.
- Provided materials to RNAssist for further in vitro and in vivo testing.
Impact
The development of TheraPHIX™ as a robust way to store vaccines without freezing or even refrigeration could revolutionise the global distribution of vaccines.
CPI’s expertise in formulation, biologics and RNA technology was essential for testing and optimising DES formulations as options for inclusion within RNA-LNPs or as a protective outer layer. Having two methods for DES incorporation gives RNA vaccine and therapeutic manufacturers flexibility when deciding at what point and how to incorporate the DES into their formulation.
The success of CPI’s collaboration on TheraPHIX™ has resulted in RNAssist filing intellectual property (IP) patents for the application of this technology and launching a range of stabilisation reagents for RNA-LNPs to the market.
RNA vaccine manufacturers using TheraPHIX™ will be able to keep vaccines viable at ambient temperatures, removing the need to use large, heavy refrigeration units and freezers on their journeys into tropical and equatorial countries with high heat and humidity. This could radically increase vaccine coverage in isolated communities in lower- and middle-income countries, ultimately improving vaccine equity.
The COVID-19 pandemic showed we have the tools to vaccinate countless people worldwide. The challenge is getting them into the hard-to-reach communities. Our work with RNAssist on TheraPHIX™ has the potential to improve the lives of even more people worldwide and halt the spread of future epidemics or pandemics faster.
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