In this article, Vincenza Pironti, Head of Business Development at Recipharm, explores the latest trends in messenger RNA (mRNA) drug development, dives into the development challenges this modality poses, and explains how lyophilisation can hold the key to optimising stability in storage and transit
The mRNA therapeutics market was estimated to be worth $18.7 billion in 2023, and is forecast to grow to $40 billion by 2033, expanding at a compound annual growth rate (CAGR) of 8.2% throughout the forecast period.
Stability is a Hurdle
While mRNA therapeutics offer a number of benefits for pharmaceutical companies seeking novel solutions for currently untreatable diseases, they do present challenges in development and manufacturing. These need to be addressed to deliver an effective and commercially viable end product.
A particular problem for mRNA-based therapeutics is their inherent instability. The mRNA molecule is naturally both physically and chemically unstable:
• Physical instability concerns include the loss of secondary or tertiary structure, as well as aggregation and precipitation, which affect the translation of mRNA molecules.
• Chemical instability issues include potential degradation due to hydrolysis and oxidation.
Failure to address these issues in development can lead to a product with a short shelf life, or one that requires frozen or ultra-frozen storage and transport – as we saw with COVID-19 vaccines, some of which required storage at -70°C. These storage and shelf-life challenges can have implications for global accessibility of novel therapeutics – it may be difficult to transport doses long distances overseas, and emerging markets, where there is limited cold-chain infrastructure, may end up being underserved.
Lyophilisation Presents a Potential Solution
One possible answer to this issue for future mRNA-based vaccines, cancer treatments and other therapies is the use of lyophilisation in the formulation process. Lyophilisation or freeze-drying is a process in which water is removed from a product after it is frozen and placed under a vacuum, allowing the sublimation of water. The process consists of three separate, unique, and interdependent processes; freezing, primary drying (sublimation), and secondary drying (desorption).
The advantages of lyophilisation include:
• Enhancing the stability of highly sensitive products
• Gentle removal of water from the formulated mRNA
• Rapid and easy dissolution of reconstituted product
Lyophilisation Challenges to be Overcome To harness the benefits of lyophilisation in overcoming mRNA instability, pharmaceutical companies do need to answer a number of questions.
