As we already advanced in one of our previous publications, the mRNA vaccines used against SARS-CoV-2 are neither a coincidence nor a specific event. This field of biotechnology has been developing for years, and the pandemic has been just the trigger that has allowed us to finish polishing this technology. The Pfizer and Moderna vaccines have been the first to use mRNA, but we can be sure that they are the first of many due to the countless advantages they offer over other types of vaccines.
This revolution within the biopharmaceutical sector has a very great implication. This type of drug was not produced until a few months ago because the technology was not 100% developed. Now an immense number of doses are needed and in the near future, vaccines with very similar characteristics will begin to be used. Therefore, a new typology of production plants is required to cover all this demand. And what characteristics must a plant where this type of vaccines are produced meet? We tell you from Klinea, as engineering specialized in (bio)processes and GMP plant design.
Before starting, let’s briefly remember how mRNA vaccines work and how they act in our body. mRNA vaccines to prevent Covid-19 introduce mRNA fragments protected by a lipid envelope into our body. These fragments will reach specific cells, which will be able to interpret the information from the mRNA. The information contained in this mRNA allows our cells to produce a protein found in the SARS-CoV-2 envelope, called protein S. The S protein alone does not cause any damage, but is capable of acting as an antigen ( substance that generates immunity in our body). That is, the cells of our immune system will be able to recognize protein S and generate specific antibodies against it. In this way, if the virus were to enter our body, we would already have specific antibodies that would recognize the S protein present in the virus envelope. And the antibodies would neutralize and kill the virus before it could cause serious illness.
· The mRNA fragments. These are made up of a chain of nucleotides. Several strategies can be followed to produce mRNA. In this specific design we will use the following one. A strand of DNA, called a plasmid, will act as a “template.” The mRNA will be produced by adding nucleotides, which will be arranged in the order established by this “template”.
· Plasmids that act as a “template”. These plasmids will be produced using cells that will be grown in a fermenter. After the necessary time, the plasmids can be purified using the following operations: centrifugation, cell lysis, clarification, chromatography, enzymatic digestion, ultrafiltration/diafiltration and, finally, sterilization by filtration.
For the design of the plant, it is essential to take into account the regulations that regulate the type of medicine to be produced. Contrary to what it may initially seem, mRNA vaccines are not considered ATMPs (Advanced Therapy Medicinal Products). In the American framework, they are regulated by 21 CFR 600 – 680. Regarding the design of the plant itself, the FDA has published the following document: FDA’s Development and Licensure of Vaccines to Prevent COVID-19 Guidance for Industry (FDA-2020 -D-1137). Regarding European regulation, the conditions of Annex II would apply, as it is considered a biological medicine for human use, as well as Annex I, because it is a sterile medicine. In addition, the regulation of gene therapies is also applied (annex IV).
In an mRNA vaccine production plant we will find the following operations:
Production of the plasmid. This involves growing cells (probably bacterial) in fermenters and the subsequent purification of the plasmid mentioned above.
Production of mRNA. Using the plasmid and other components, such as nucleotides and certain enzymes, the mRNA fragments that will go into the vaccine will be produced. Once again, purification will be necessary to separate the mRNA from the other remaining elements involved in the reaction.·
Production of lipid envelope and binding with mRNA. From lipids, envelopes will be produced that will protect the mRNA until it reaches the cell. Once produced, the mRNA fragments will be encapsulated within these lipid envelopes.
These are each of the dedicated areas that go beyond “the usual” in the design of a biopharmaceutical production plant. Apart from these, there will be other more common ones among which we find: the area for the formulation of the final medicine, the warehouse for finished product (with freezers, if required), the filling area, primary and secondary packaging, and auxiliary areas, such as technical areas, buffer preparation room, weighing room, cold rooms, etc.
We are now in a moment of change, which awaits us in the design and construction of new mRNA vaccine production plants. And although, currently, there is a lot of uncertainty about certain regulatory aspects of this type of environment, the needs of the market demand that we be able to provide solutions to satisfy the growing demand. In addition, these new plants give the possibility of including very high levels of automation at the level of control and process data collection. Which represents an excellent opportunity for the biopharmaceutical sector to continue advancing along the path of industry 4.0.
If you are interested in learning more about GMP plant design and how we can help you, contact us: klinea@klinea.es
