Contract development and manufacturing organization (CDMO) Samsung Biologics recently began operations of its new mRNA vaccine production suite, which was designed to provide the CDMO’s clients with end-to-end services.
The new suite is part of Samsung Biologics’ broader commitment to end-to-end capabilities across its operations, which includes industry-leading capacity for the production of monoclonal antibodies.
In biomanufacturing, end-to-end capabilities involve providing both drug substance and drug product services.
This means that Samsung Biologics can produce the active substance in a biologic medicine, as well as transfer it to a final product that’s ready to be used by a patient.
The advantages of this one-stop-shop approach include increased efficiency, accelerated timelines, and risk mitigation.
In a recent Q&A, Pierre Catignol, Samsung Biologics’ Executive Vice President and Head of Manufacturing, and Huisub Lim, lead scientist of mRNA manufacturing, explained that, as Samsung Biologics considered expanding its mRNA vaccine production facilities, these potential advantages led it to focus on building a suite with end-to-end capabilities.
“Few manufacturers/CDMOs are adequately equipped or capable of carrying out all manufacturing steps, leading to logistical, monetary, and timeline difficulties. Frequent handling of mRNA across multiple locations increases contamination and degradation risks.
When the entire work stream is coordinated by one partner, from a single location, transitions across development and production tasks run smoothly, maximizing efficiency and mitigating potential risks.”
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mRNA Vaccine Production Background
mRNA technology had been the subject of research for decades leading up to the beginning of the COVID-19 pandemic in 2020.
Researchers had long recognized the potential for mRNA, single-strand molecules encoded via DNA to instruct cells’ ribosomes to create proteins. The encoding process enables mRNA molecules to be easily edited and manufactured on faster timelines than traditional vaccines.
mRNA vaccine production doesn’t require growing a virus to use as the active substance; rather than stimulate an immune response by infecting the body with a small portion of a virus, mRNA instructs cells to create noninfectious targeted proteins that combat a virus.
This means that mRNA vaccine developers can avoid the time-consuming process of growing a virus in cells or chicken eggs and can quickly edit and share information on the structure of mRNA molecules required to target a specific virus. This is particularly useful for inoculating against potentially fast-mutating viruses such as COVID-19.
While these potential benefits tantalized researchers and biomanufacturers looking for innovative solutions to combat viruses, concerns remained about the stability of mRNA molecules.
Researchers needed to develop a way to ensure that the mRNA molecules used for vaccines didn’t degrade when transferred to vaccine vials and injected into the body.
In the years leading up to the pandemic, significant progress was made on this front through the development of lipid nanoparticle (LNP) coatings that protect mRNA molecules from degradation.
mRNA vaccine production research was accelerated with the onset of COVID-19, eventually leading to the first approved mRNA vaccines. As a CDMO, Samsung Biologics partnered with Moderna to produce these vaccines, providing aseptic fill/finish services for Moderna’s COVID-19 mRNA vaccine.
“Samsung Biologics was the first in Korea to perform fill/finish manufacturing of Moderna’s COVID-19 mRNA vaccine and obtain approval from the Korean Ministry of Food and Drug Safety (MFDS),” explained Samsung Biologics president and CEO John Rim in the CDMO’s 2022 letter to shareholders.
“Samsung Biologics will continue to dedicate itself to providing a reliable supply of COVID-19 vaccines and treatments and contribute to the ending of the prolonged COVID-19 global pandemic.”
Samsung Biologics’ mRNA Drug Substance and Drug Product Capabilities
Its mRNA vaccine production partnership with Moderna didn’t require Samsung Biologics to produce the active drug substance for the vaccines at its facilities. However, recognizing the potential of an end-to-end mRNA suite at a single location, the CDMO added mRNA drug substance capabilities for future projects.
These capabilities were exhibited earlier this year with Samsung Biologics’ completion of the first commercial-scale manufacturing run of GreenLight Biosciences’ COVID-19 mRNA vaccine candidate.
“This demonstrates a major achievement in our continuing goal to offer one-stop, end-to-end mRNA production from drug substance to aseptic fill/finish to commercial release, all from a single site, as we strive across our biomanufacturing network to fight the pandemic,” said Rim in a press release on the production run.
The project demonstrated Samsung Biologics’ ability to handle the production of mRNA molecules, LNP formulation, and drug product services from a single facility.
For mRNA vaccine production, the drug substance process involves linearizing circular plasmid DNA (pDNA) molecules and transcribing them into mRNA using enzymes and nucleotides in a reactor.
The resulting mRNA molecules are then purified through chromatography and ultrafiltration and, using precise pump mixing technology, encapsulated in LNPs produced at the same facility.
The drug product process involves transferring this mRNA drug substance into sterile vials, ensuring that they aren’t contaminated throughout an aseptic fill/finish process carried out in cleanroom environments.
MRNA requires a precise temperature-controlled process, and Samsung Biologics utilizes cold storage facilities with capabilities of reaching temperatures as low as minus 70 degrees Celsius.
For Samsung Biologics, a central goal of end-to-end mRNA vaccine production is to offer clients the ability to rapidly scale up manufacturing as needed, and they’ve designed their mRNA drug substance and drug product services to be able to accommodate projects of a variety of scales.
“Dedicated manufacturing slot availability, guided by a well-established agreement, is key to agility,” explained Catignol and Lim. “Equally important is capacity within that slot: specifically, the capability to manufacture at varying scales, from small, clinical-stage batches (milligram scale) to high-volume commercial (up to 200-L scale).”
For GreenLight Biosciences, Samsung Biologics’ ability to quickly scale mRNA vaccine production to reach commercialization was crucial.
“One of the greatest challenges when producing quality pharmaceuticals is advancing from a small lab to large-scale commercial production,” said GreenLight CEO Andrey Zarur.
“We are grateful for the help and support of Samsung in demonstrating that our small mRNA process can scale in a linear fashion to the industrial scale that will be needed to help satisfy the vaccine needs of humanity.”
Catignol and Lim explained that Samsung Biologics’ commitment to high-volume capacity in mRNA vaccine production is simply the next step for a CDMO that’s made expanding capacity a central pillar of its business plan, along with entering innovative areas of biomanufacturing with potential to grow.
In addition to mRNA, these areas include biosimilars and cell and gene therapies.
“Not many CDMOs offer the high-volume capacity to manufacture mRNA products. Samsung Biologics has invested in this capacity because we know mRNA is an expanding field in both prominence and opportunity,” said Catignol and Lim.
“Among a CDMO’s most important responsibilities are constant vigilance and preparedness, the ability to read the needs of the market, and to be ready to fulfill public and industry demands when required.”