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The Storage and In-Use Stability of mRNA Vaccines and Therapeutics: Not A Cold Case
Erik Oude Blenke1, Eivor Örnskov1, Christian Schöneich2
1Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, 43183 Gothenburg, Sweden.
Journal of Pharmaceutical Sciences
|November 9, 2022
Summary
Improving messenger RNA (mRNA) stability is crucial for vaccine and therapeutic development. This review details strategies to overcome storage limitations, enabling refrigerator storage instead of frozen conditions.
Area of Science:
- Biotechnology and Pharmaceutical Sciences
- Vaccine Development and Delivery
- Drug Formulation and Stability
Background:
- Messenger RNA (mRNA) vaccines demonstrated significant public health impact during the COVID-19 pandemic.
- Current mRNA therapeutics and vaccines require frozen storage due to inherent stability limitations.
- Advancements in mRNA technology are hindered by challenges in achieving long-term stability at refrigerator temperatures.
Purpose of the Study:
- To provide an update on strategies for enhancing mRNA stability for vaccine and therapeutic applications.
- To address the multifaceted challenges in improving formulated mRNA stability for broader accessibility.
- To explore methods enabling refrigerator storage of mRNA-based products.
Main Methods:
- Review of chemical degradation pathways of mRNA during storage.
- Analysis of lipid nanoparticle (LNP) formulations as both protective agents and sources of instability.
- Discussion of strategies targeting mRNA molecule design, physical state, formulation composition, and manufacturing processes.
- Summary of analytical control strategies for monitoring mRNA stability.
Main Results:
- Lipid nanoparticle (LNP) formulations offer protection against enzymatic degradation but can introduce new instability risks through excipient interactions.
- Strategies for enhancing mRNA stability include optimizing mRNA structure (nucleotide selection, sequence, and folding), controlling the physical state of mRNA-LNP complexes, ensuring formulation purity, and refining manufacturing processes.
- Integrated analytical and formulation development is key to improving storage, transport, and in-use stability.
Conclusions:
- Overcoming mRNA stability limitations is essential for the widespread application of mRNA vaccines and therapeutics.
- A comprehensive approach integrating molecular design, formulation science, and manufacturing is required to achieve stable mRNA drug products.
- Future development should focus on enabling refrigerator storage conditions for mRNA-based candidates through advanced stability strategies.
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