The launch of two mRNA vaccines in 2020 marked the formal entry of mRNA technology into the commercial era. Strong vaccine demand is expected to bring bright prospects to the entire industry chain, and mRNA is expected to enter a golden decade of rapid development. The principles of mRNA technology apply not only to vaccines, but also to drugs and other fields. In this article, we will use mRNA vaccines as an example to discuss the entire process of mRNA vaccine production and the key links in the industry chain.
Step 1: Extract DNA from cold storage
The production personnel will extract the Coronavirus DNA from the main cell bank. The extracted DNA will be stored in a small experimental bottle at -150°C by technicians.
The technicians will then inject the thawed plasmids into a batch of engineered E. coli, causing the E. coli to take the plasmid into its own cells.
Step 2: Promote cell growth and reproduction
The cells containing E. coli and plasmids will be placed in an experimental bottle and grown and propagated in a warm sterile amber growth medium.
Step 3: Fermenting mixture (bacteria)
The above-mentioned bacteria will be given one night to propagate and reproduce before being transferred to a nutrient solution for four days to allow for bacterial growth and DNA replication.
Step 4: Purify and collect DNA
After four days of fermentation, a chemical will be injected to decompose the bacterial cell wall. The mixture will then be purified, and the remaining plasmids extracted.
Step 5: Quality inspection
The extracted plasmids will be compared with previous samples by technicians to confirm whether the virus gene sequence of the newly produced plasmids can be used for vaccine production.
Step 6: Plasmid linearization
After quality inspection, enzymes will be added to cut circular plasmids into linear segments.
Step 7: DNA purification
Technicians will purify the mixture again, which is already of high purity, in order to filter out any residual bacteria or plasmid fragments.
Step 8: Transport
Before transportation, each bottle of DNA will be frozen, bagged, sealed, and then placed in a container with enough dry ice. These containers will be transported to another factory for transcription.
Step 9: DNA conversion to mRNA
The transported DNA will be thawed and mixed with a partially composed mRNA solution. Enzymes open the DNA template and convert it to mRNA.
The resulting mixture will then be moved into a tank and filtered to remove impurities.
Step 10: mRNA testing
The filtered mRNA will be repeatedly tested to ensure gene sequence precision and accuracy.
Step 11: Refrigeration, packaging, and transportation again
The tested mRNA will be frozen at -20°C and shipped to factories where the vaccine will be produced. Samples will be tested after production.
Step 12: Preparing the mRNA
After receiving the package, the mRNA will be frozen until needed. Each batch can produce 600,000 bottles and a total of 3.6 million doses of vaccine.
Step 13: Lipid Preparation
At the same time, another step is underway to prepare lipids, which protect mRNA from being destroyed when it enters human cells.
Step 14: Producing mRNA vaccines
Once prepared, machines mix mRNA and lipids under precise control to produce lipid nanoparticles, forming vaccine particles.
Step 15: Preparation of vaccine bottles
Vaccine bottles are cleaned and sterilized at high temperatures, and 13 high-speed cameras monitor the production line. Each bottle is photographed more than 100 times, and any bottle with cracks, fragments, or other issues will be quickly screened out of the production line.
Step 16: Filling vaccine bottles
The machine injects 0.45 ml of vaccine into a bottle, which, after being diluted, becomes a vaccine in six doses. The production line packages 575 bottles per minute.
Step 17: Packaging, refrigeration, and testing
The filled vaccine is inspected, labeled, and packaged in boxes. All boxes will be frozen for several days, cooling to an extremely cold temperature of -70°C. At the same time, this batch of vaccines will be sent for testing.
Step 18: Packaging and transportation of finished vaccines
After several weeks of testing, qualified vaccines can be transported. Each box is equipped with a thermometer to monitor temperature in real time. Each box contains 45 pounds of dry ice.
In summary, the mRNA technology research and development wave has led to a medical revolution for new therapies. However, the mRNA industry still needs to be improved due to its late start. There is relatively little completeness and matching between the upstream, downstream, and middle segments of the industry chain. How to produce mRNA products in large quantities and rapidly is a critical issue for industry practitioners. As a leading chemical supplier, BOC Sciences has taken every effort to help supply the raw materials for mRNA vaccine.