In the pharmaceutical industry, mRNA vaccine production has become a popular topic, especially in the context of COVID-19. But in addition to its use in COVID vaccines, mRNA technology has shown promising results in the development of vaccines for other diseases. The success of COVID mRNA vaccines has catalyzed a revolution in mRNA vaccine production and research, with over 1,800 clinical studies on mRNA listed in the U.S. National Library of Medicine database.
At Samsung Biologics, one of the world’s largest contract development and manufacturing organizations (CDMOs), scientists and manufacturing experts are working to play a leading role in this revolution, building end-to-end mRNA vaccine production capabilities to work with partners at a variety of development and manufacturing scales.
“With relatively simple editing, mRNA can offer ‘plug-and-play’ applications,” explained Jeong Jin-hyeok, head of inspection and packaging at Samsung Biologics, in a recent article. “This characteristic has opened the door to their use in various therapeutic areas. MRNA technologies currently in the development pipeline include those that target rare diseases, autoimmune disorders, and various cancers.”
He went on to explain that this onset of research and development has led experts to predict the mRNA vaccine production market will continue to grow. According to Jin-hyeok, the market is expected to increase from $46.7 billion in 2021 to $101.3 billion in 2026, increasing at a compound annual growth rate of 16.8%.
To accommodate growing demand for innovative mRNA vaccines and therapies, Samsung Biologics has focused on expanding its mRNA vaccine production capabilities since partnering with Moderna in 2021 to produce COVID mRNA vaccines. The CDMO now offers both drug substance and drug product services at a single location at its headquarters in Songdo, South Korea.
“For COVID-19 mRNA vaccines in the market, production of mRNA drug substance, encapsulated (LNP) final product, and fill/finish activities have often been conducted at different sites, increasing the risk of contamination, time, and cost,” said Samsung Biologics’ Esther Yoo, in a recent white paper. “Samsung Biologics’ mRNA facility provides end-to-end solutions from pDNA linearization to fill/finish, all under one roof.”
How Does mRNA Vaccine Production Work?
Traditional vaccines involve growing a virus or bacteria in cell cultures. But mRNA vaccine production involves synthesizing a piece of genetic material, mRNA, in a laboratory via an in vitro, or cell-free, process.
The mRNA contained in a vaccine instructs the body to produce a protein that triggers an immune response to the target virus. For example, COVID mRNA vaccines enable the body to produce the spike protein found on the surface of the SARS-CoV-2 virus, which is the underlying cause of COVID-19.
When it comes to producing these targeted mRNA vaccines, there are several key steps that require specialized equipment. Samsung Biologics covers all these steps using the equipment at its end-to-end facility.
First, the mRNA must be properly sequenced to construct the protein required. This process involves identifying the specific amino acid sequence of the protein and encoding this sequence into an mRNA molecule. Sequencing can be conducted digitally and information can be quickly shared, scaled, and adjusted as needed.
Once the proper sequence is identified, the molecule must be synthesized and encapsulated in lipid nanoparticles to prevent degradation. For Samsung Biologics, this process involves linearizing plasmid DNA (pDNA), which is then used to encode the mRNA molecules. The mRNA is purified and capped using enzymes and transferred to a final drug product through an aseptic fill/finish process that requires precise clean-room conditions and filters. Cold chain storage ensures the mRNA is maintained at the proper temperature to ensure stability.
Jin-hyeok explained that adapting cold chain storage and aseptic fill/finish processes to mRNA was one of the most pressing challenges for mRNA vaccine production during the pandemic. Samsung Biologics has refined its processes as an experienced fill/finish provider for Moderna. It provides upright and walk-in cold chain storage systems with temperatures as low as minus 70 degrees Celsius.
New Applications for mRNA
While all current mRNA vaccine production projects have focused on COVID-19 vaccines, there are several exciting new therapeutics possibilities for mRNA.
“Nearly 60% of candidates target solid tumors, while 30% of candidates are vaccines,” explained Yoo. “The remainder are treatments for diseases such as colorectal cancer, Lyme disease, and autoimmune diseases. MRNA is also being investigated as a potential nonviral delivery system for gene therapies.”
MRNA vaccines can be designed to produce specific proteins found in cancer cells, which can then trigger an immune response against those cells. In the case of personalized vaccines, using a patient’s genetic information to design mRNA vaccines or therapies could improve their effectiveness and reduce the risk of adverse reactions.
Researchers are exploring the use of mRNA vaccines to target viruses, such as HIV, Zika, influenza, and respiratory syncytial virus (aka RSV), a common cause of respiratory infections in young children and the elderly.
MRNA therapies can also be designed to produce functional copies of genes that are mutated or missing in patients with genetic disorders. This technique could be used to treat rare diseases such as cystic fibrosis and Huntington’s disease.
For Samsung Biologics, the outlook for the future of mRNA vaccine production is bright, with the potential for significant improvements in the treatment of a wide range of diseases.