mRNA vaccine stability and storage

mRNA vaccine stability and storage.  mRNA vaccine technology is one of the new vaccine technologies that have been gradually developed in recent years, and its technologies in terms of efficient delivery have become increasingly mature.

The mRNA vaccine expresses antigens in cells, and can prevent infectious diseases by stimulating the immune system to produce B and T cell immune responses and other effective mechanisms. At the same time, because it is a fully synthetic preparation, the production process is simple, and it has the potential to quickly respond to sudden infectious diseases such as new coronavirus infection.

The new coronavirus pneumonia vaccine currently being tested, due to the use of mRNA technology, must be stored at a low temperature of -70°C from bottling to the moment before the patient is vaccinated. Compared with the storage requirement of 2°C~8°C required by ordinary vaccines, the COVID-19 vaccine is more sensitive to temperature. The mRNA vaccines currently developed by Pfizer and BioNTech must be stored at a low temperature of -70°C from bottling to the moment before the patient is vaccinated. To ensure foolproofness, Cold Chain Logistics sets the cold chain limit temperature target as low as -80°C. Even companies that are in a leading position in the research and development of COVID-19 vaccines are facing the challenge of the ultra-low temperature environment required for vaccine storage and transportation.

Even if the vaccine stays outside the specified temperature range for an extremely short period of time, there is a great risk of deterioration. A study by the World Health Organization (WHO) estimates that up to 50% of vaccines worldwide are wasted every year, largely due to the lack of temperature control and logistics to maintain a complete cold chain. WHO, FDA 21 CFR Part11, GxP and other food and drug transportation regulations have specific regulatory requirements for vaccine cold chain temperature control. To meet the requirements of relevant regulations and ensure the safety of vaccines, vaccine transportation and storage must be supported by a mature cold chain system.

The mRNA vaccine itself is unstable and easily degraded. In addition to improving the stability of the mRNA by improving the sequence of the 5’UTR and 3’UTR regions, synthesizing a “cap”-like structure, and modifying the poly A tail, more efficient methods of mRNA delivery are used to avoid its degradation. Delivery vectors can significantly improve the stability and translation efficiency of mRNA vaccines. Commonly used delivery vectors can be divided into viral vectors and non-viral vectors. Research teams from the Netherlands and the United States have conducted research on the instability and ultra-low temperature storage characteristics of mRNA vaccines.

Table 1: Current stability profile, dosage and dosage schedule of mRNA COVID-19 vaccine candidates in development (as of December 05, 2020)

However, researchers have found that there is very little information about the stability of mRNA drug products, that is, the stability and storage of LNP-mRNA and protein-mRNA complexes.
However, they found little information: a candidate for an mRNA-protein amine vaccine against rabies was freeze-dried and tested in mice. Store dry at a temperature of ±80 to +70°C. Under the selected readout conditions (1 vaccine dose level), the vaccine stored at 5, 25, 37 and 45°C for 12 months can fully neutralize antibody levels and protect mice from rabies infection. Even after 3 months of storage at +70°C, protection of the mice was observed. Unfortunately, this study did not provide relevant details or physicochemical quality attributes before and after the Haemophilus and storage.
In addition, the European Union’s drug test files also pointed out that the stability indicator parameters of mRNA components are: mRNA integrity, content and potency, as well as drug characteristics, including pH, appearance and microbial status of drug products.

Table 2: Shows two mRNA COVID-19 vaccine candidates as qualitative components formulated as mRNA-LNP. Through a series of analysis methods, the identity, purity, potency, safety and stability of mRNA biological activity and mRNA lipid/protein composite formula were analyzed.

The researchers also reviewed the key technologies currently available to monitor the key quality characteristics of mRNA vaccine candidates (Table 3). They expanded the list to include additional tests and attributes related to mRNA drug products. Unfortunately, the critical review of analytical techniques to describe mRNA-(cation) lipid complexes, such as previously published information on plasmid DNA lipid complexes, is not so sufficient.

The two most interesting issues of mRNA are immunogenicity and stability. After chemical modification of selected nucleotides, these issues are controlled to a certain extent. As other RNA drugs (ASO and RNAi) are approved, the field of mRNA research will become more popular once more positive data is released. There may be many problems with mRNA in the short term, but in the long term, this is definitely worth exploring.

(source:internet, reference only)

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