MRNA vaccine production methods have evolved at a rapid pace since the onset of the COVID-19 pandemic. With the accelerated approval of the first mRNA vaccines during the pandemic, manufacturers had to quickly adapt to new technologies and produce vaccines at a massive scale.
For Samsung Biologics, a contract development and manufacturing organization that partnered with Moderna to manufacture COVID mRNA vaccines, the key to adapting to this new environment has been leveraging prior manufacturing expertise and applying it to new challenges unique to mRNA. Two prime examples of this approach are the CDMO’s cold chain storage and fill/finish solutions for mRNA vaccine production.
“Those organizations that responded to meet rising fill/finish and cold chain capability demands are well-positioned to handle the predicted rise in mRNA production needs in the future,” explained Jeong Jin-hyeok, head of inspection and packaging at Samsung Biologics, in a recent article. “CDMOs with these adapted capabilities will also be aligned to support another area in biopharma expected to see expansion: the cell and gene therapy (CGT) space.”
What Is Cold Chain Storage?
Cold chain storage refers to the process of maintaining vaccines and other biologics at specific low temperatures during transportation, storage, and distribution to ensure their potency and efficacy. For mRNA vaccines, which are highly sensitive to temperature fluctuations, cold chain storage is particularly important to maintain the stability and integrity of mRNA molecules.
One of the primary challenges facing mRNA vaccine production is the need for cold chain storage throughout the entire manufacturing process, from the production of the mRNA molecules to the final distribution of the vaccines. The mRNA molecules can quickly degrade or lose efficacy if not stored and transported under precise temperature conditions. This requires specialized cold storage equipment and infrastructure, as well as trained personnel to manage the process.
Samsung Biologics has addressed this challenge by offering upright and walk-in storage systems with temperatures as low as minus 70 degrees Celsius. It’s also added drug substance capabilities to give clients end-to-end mRNA vaccine production options. Providing drug substance and drug product services in a single facility mitigates the challenge of maintaining cold storage conditions in transport.
“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 Esther Yoo from Samsung Biologics in a recent white paper. “Samsung Biologics’ mRNA facility provides end-to-end solutions from pDNA linearization to fill/finish.”
What Are Fill/Finish Services?
Fill/finish services are provided at the final stages of mRNA vaccine production. They include filling, labeling, packaging, and distribution.
In the case of mRNA, fill/finish requires specialized equipment and expertise to ensure the stability and sterility of the product. The mRNA vaccines require careful handling during the filling and packaging process to avoid any damage to the fragile mRNA molecules or contamination from other sources. Handling the vaccines involves advanced technology and rigorous quality control measures.
“Ensuring sterility of biotherapeutics is often achieved using sterile filtration, as this is often the only method that can suitably sterilize the product without affecting its stability,” said Jin-hyeok. “Typically, sterile filtration is achieved using two in-line filters during fill/finish that are placed in Grade A environments as close to the filling points (needles) as possible. In this way, the product is sterilized as it flows through the lines to a container closure.”
The Future of mRNA Vaccine Production
The development of mRNA vaccines has prompted investment in new technologies and infrastructure to support the production and distribution of these vaccines. This has led to advances in cold storage equipment and technology, as well as new fill/finish systems designed specifically for mRNA vaccines.
These technologies will be crucial as mRNA vaccine production advances beyond COVID-19 applications. The biopharmaceutical industry is optimistic about new applications, which include vaccines to treat cancer, autoimmune disorders, and other infectious diseases such as HIV and influenza.
Jin-hyeok highlighted that the global market for mRNA therapeutics is expected to reach $101.3 billion by 2026, increasing from $46.7 billion in 2021 at a compound annual growth rate of 16.8%. Much of this growth will be in non-COVID mRNA vaccines. Yoo noted that over 1,800 clinical studies involving mRNA were listed in the U.S. National Library of Medicine database as of summer 2021, with roughly 60% focused on targeting solid-state tumors with mRNA and 30% focused on preventive vaccines.
To support this growth in mRNA vaccine production, experts have emphasized the importance of robust infrastructure, innovative technology, and skilled personnel to ensure quality, safety, and efficacy.
“When examining the lessons from the early years of COVID-19’s onset, it is clear that flexibility and adaptability were essential for CDMOs to successfully provide cold chain and fill/finish capabilities for mRNA vaccine production,” said Jin-hyeok. “By reflecting on these lessons, manufacturers can be confident in their approach to supporting mRNA projects under pressure and be prepared for a variety of new challenges that could be predicted on the horizon.”
