Advantages of mRNA Vaccine Technology

Based on the article:

How to Make Enough Vaccine for the World in One Year



Reprinted for educational purposes and social benefit, not for profit. 

Critically, mRNA vaccines offer several advantages over other vaccine platform technologies.

Conventional cell-based expression technologies require growing cells in large bioreactors (e.g., 2000L), which depends on a careful optimization of biological conditions. Cells introduce some variability. While mRNA production uses a novel process, it is cell-free and more akin to biochemical synthesis. There are at least seven distinct advantages:

1. The process is simpler.

mRNA vaccine production requires fewer steps compared to cell-based vaccine production, especially in the upstream processing section. The mRNA vaccine production reaction mix also uses fewer and more well-defined components compared to cell-based vaccine production as the mRNA vaccine production reaction mix does not contain nutrients for cells, cell debris, proteins, chromosomal DNA, lipids and complex sugars that cells release.[12] This simplicity of the reaction mix in turn reduces the complexities in the downstream purification process.[13]

2. The process is more robust.

Once the mRNA vaccine production process is established, there is also less potential for biological variability. Living cells perform complex, interconnected functions. They can sometimes behave unpredictably, leading to unexpected results such as reduction in production yields.[14] mRNA vaccine production can largely bypass this complexity.

3. Dose production is faster.

The production of the vaccine active ingredient, the mRNA molecule, can be completed in two to six hours. The entire production batch for mRNA vaccines, including the enzymatic synthesis of the mRNA, purification, and formulation, can be completed within days, excluding the time required for quality control testing.[15] For example, BioNTech produces batches at three to seven day intervals, with four to five weeks spent for quality control.[16] In contrast, completing batches for cell-based vaccines can take several months due to the time required to grow the cells to the specified volumes and quantities.[17] The productivity of the mRNA vaccine production, expressed in doses per L of bioreactor working volumes per day, is two to four orders of magnitude higher compared to most cell-based vaccine production processes.[18]

4. The facilities and equipment can be an order of magnitude smaller.

mRNA vaccine production can take place in much smaller bioreactors (e.g., 30L to 50L) than those generally employed in cell-based vaccine production (e.g., 2000L).[19] While mRNA vaccine production can require high volume buffer solutions, the smaller scale of the mRNA vaccine production process means it can be implemented in smaller facilities. Multiple mRNA vaccine production processes, for example, can be placed into a conventional cell-based vaccine production facility.

5. The capital costs are lower.

Given the small-scale nature, setting up the production process and covering facility related expenses is cheaper for mRNA vaccines.

6. The process can be implemented in more existing facilities.

The number of existing facilities that can accommodate mRNA vaccine production is higher than the number of facilities that can be used generally for setting up new cell-based vaccine production processes. In addition to its small-scale nature, mRNA vaccine production can be hermetically sealed from the environment.[20] This can allow production in lower grade clean rooms.[21] mRNA vaccine production processes can in principle be set up in clean rooms in existing facilities that are used to produce other vaccines, monoclonal antibodies, insulin, veterinary vaccines, and other biologics and injectables.

7. The process can be quickly repurposed for new variants, or even new viral threats.

mRNA vaccines involve rapid development and production timelines because the production platform is agnostic to the disease target. Different RNA sequences translating into different vaccine or candidate vaccine protein antigen can be produced using the same process.[22] The only component in this production process that needs to be changed is the template DNA based on which the RNA is enzymatically synthesized. The rest of the materials, equipment, consumables, unit operations, formulation components, fill and finish processes as well as quality control and quality assurance methods remain unchanged when switching to the production of a new RNA sequence encoding for a new vaccine antigen. This flexibility can help ensure long-term sustainability.