How Does a CDMO Avoid mRNA Vaccine Production Bottlenecks? Experts at Samsung Biologics Explain

CDMO

MRNA vaccine production is a relatively recent development, with the first approved mRNA vaccines produced to treat COVID-19 in 2021. However, mRNA technology is undergoing a period of significant evolution, and it’s expected that mRNA vaccines will be developed for a variety of applications, from cancer to heart disease, in the coming years. As the technology develops, Samsung Biologics, one of the world’s largest contract development and manufacturing organizations, has developed methods that avoid manufacturing bottlenecks and can produce mRNA vaccines at a variety of scales.

The CDMO’s approach, as Samsung Biologics executive vice president and head of manufacturing Pierre Catignol explained in a recent white paper, is to provide end-to-end mRNA vaccine production services at a single facility.

“The key for mRNA therapy and vaccine developers will be to find a CDMO with the capability to provide end-to-end support for mRNA projects. Samsung Biologics is applying the Power of One to mRNA, investing in a one-stop solution to facilitate the advance of customer mRNA molecules from the clinic to commercialization, including product and process development and characterization.”

How Does mRNA Vaccine Production Work? 

MRNA vaccine production has many advantages over traditional vaccine development methods.

Traditional vaccines work by injecting a small portion of the target virus (or a virus that’s sufficiently similar to the target) into the body to produce an immune response. By contrast, mRNA vaccines work by injecting mRNA molecules that have been encoded with genetic information to instruct the body to produce disease-fighting proteins.

This means that mRNA vaccine production doesn’t require the time-consuming and costly process of using living cells to grow a virus in a lab, and mRNA vaccines can be quickly and easily edited in a way in which traditional vaccines cannot. In addition, mRNA vaccines can be edited to achieve high degrees of specificity in terms of the diseases they target. For example, researchers are working on developing personalized cancer vaccines that rely on mRNA to target the unique cancer of an individual patient.

However, these advantages don’t mean that mRNA vaccine production is without challenges. The process involves several complex steps, including linearizing circular strands of plasmid DNA (pDNA), transcribing the genetic information from these molecules onto mRNA molecules in an in vitro (cell-free) process, then purifying and encapsulating the mRNA molecule in lipid nanoparticles to ensure stability. MRNA must also be kept at precise cold temperatures to avoid degradation, which requires advanced cold chain storage capabilities.

In addition, the high degree of specificity that makes mRNA vaccines an ideal technology for personalized vaccines also means that some vaccines will require very small manufacturing batches, potentially as small as a single vaccine for a personalized cancer vaccine. On the other hand, vaccines for more widespread conditions, such as those used to prevent COVID-19, require large-scale production of thousands of doses at a time.

As Catignol explains, this disparity provides a unique manufacturing challenge that requires an adept CDMO with diverse scaling capabilities.

“To date, mRNA manufacturing at large scale has taken place in bioreactors with capacities of less than a hundred liters at most. That scale can provide millions of doses of an mRNA vaccine. Many mRNA candidates in development are intended to treat much smaller patient populations compared with a global vaccine,” wrote Catignol. “Accordingly, production capability will be needed at scales from milliliters to several hundreds of liters. The question for mRNA manufacturing, therefore, is not just one of achieving cost-effective scale-up but also of realizing cost-effective product at small scale and, potentially, cost-effective scale-out, which requires a unique approach.”

How Samsung Ramped Up Production

For Samsung Biologics, this unique approach involves applying the insights and expertise it’s developed as a premier manufacturer of antibodies at a variety of scales, and, crucially, building the capabilities to provide both drug substance and drug product services for mRNA vaccine production at a single facility.

The CDMO is also one of the few manufacturers that already has an established track record with mRNA vaccine production, as it provided fill/finish services for Moderna’s COVID-19 vaccine in 2021. Samsung Biologics has decided to build on this experience by expanding its mRNA capabilities, launching its end-to-end mRNA vaccine production suite in Songdo, South Korea, in April 2022.

 

These expanded capabilities have already been put to use, with Samsung Biologics completing the first commercial-scale production run of an mRNA vaccine developed by GreenLight Biosciences in August 2022. The production run produced over 650 grams of mRNA and was completed just seven months after the initial technology transfer began.

“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 in a press release announcing the completion of the production run. “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.”

While one of the advantages of a one-stop-shop approach to mRNA vaccine production is the speed at which projects can scale, another advantage, as Catignol explains, is improved risk mitigation, as the product avoids the chance of degradation that can occur in transit.

“Frequent handling of mRNA in multiple locations increases contamination and degradation risks, but when the entire work stream from pDNA to vial is coordinated by one partner from a single location, transitions across development and production tasks run smoothly, maximizing efficiency, and eliminating these potential risks,” writes Catignol. “Samsung Biologics offers integrated manufacturing services from clinical to commercial, including aseptic fill/finish, labeling, packaging, and cold chain storage — all at a single site — to successfully manufacture mRNA therapeutics.”

The field of mRNA vaccine production is still in nascent stages, but in developing its end-to-end capabilities and an approach that is adaptable to a variety of scales, Samsung Biologics will look to lead the way in efficient mRNA manufacturing as new applications emerge.