SFF
Lyophilisation plays a crucial role in addressing stability concerns associated with mRNA therapeutics. Also known as freeze-drying, the lyophilisation process enables drug products to be transported and stored without relying on ultracold chain infrastructure.
However, pharmaceutical companies face several obstacles in effectively harnessing the benefits of lyophilisation to increase the stability of mRNA products, including:
- The deformation of lipid nanoparticles
- mRNA breakage
- Reduced transfection efficiency
Overcoming these obstacles requires companies to:
- Optimise lyophilisation process development: One strategy involves optimising the lyophilisation process itself. This includes conducting a thorough study of each freeze-drying phase rather than using accelerated methods that may save time but risk damaging the formulated mRNA. By following a mild lyophilisation process, companies can better preserve the integrity and stability of the mRNA, enhancing the effectiveness of the finished therapy.
- Make formulation changes: Another approach involves making changes to the formulation itself. Modifying the ionic strength of the buffer used in the formulation can significantly impact the resulting cake post-lyophilisation. Adjusting the concentration of the mRNA before lyophilisation is also important to optimising the freeze-drying process. These formulation adjustments help ensure the effectiveness of the lyophilisation process and enhance the stability and reconstitution properties of the mRNA product.
- Assess LNP stability: Since many mRNA-based therapies employ LNP technology, it is crucial to consider the stability of LNPs during lyophilisation. It is essential to choose the right surfactant to address potential challenges that may arise, such as the aggregation of LNPs. By carefully selecting surfactants, pharma companies can better improve the stability of LNPs, leading to better overall performance and efficacy of the final mRNA product.
- Avoid structural changes to RNA: It is important to note that altering the structure of RNA is not a viable strategy to overcome the challenges associated with lyophilisation, as this could potentially undermine the efficacy of the therapy. Instead, strategies should focus on optimising the lyophilisation process, formulation adjustments and considerations for LNP stability while preserving the integrity of the RNA structure.
In our recent Q&A discussion with BioPharm International, Vincenza Pironti, Strategic Marketing Director at Recipharm, shared her expert insights on harnessing lyophilisation techniques to increase the stability of mRNA products. She also discussed the advancements made to the lyophilisation process in recent years, as well as the importance of working with an expert CDMO with experience in this area.