For a contract development and manufacturing organization, the capability to produce biopharmaceuticals at a variety of scales is crucial. CDMOs partner with a range of pharmaceutical companies from smaller specialty companies to larger multinational corporations. A CDMO’s job is to meet the unique needs of each partner, ranging from manufacturing small clinical trial batches to commercial-scale runs.

Samsung Biologics, one of the world’s largest CDMOs, has expertise in scaling projects in monoclonal antibodies. The company is now applying that expertise to mRNA vaccine production.

MRNA vaccine production is an in vitro process, meaning it does not require growing a virus or bacteria in living cells. As such, it’s typically much easier to scale mRNA projects once an effective genetic sequence for a vaccine is identified. The scalability of mRNA vaccines is one of the technology’s key benefits, and a major reason why scientists implemented it to address the COVID-19 pandemic.

Now, as researchers make significant progress on applying mRNA technology to applications beyond COVID-19, Samsung Biologics has implemented an end-to-end mRNA vaccine production suite that prepares it to partner with companies pursuing mRNA vaccine production at a variety of scales.

In a recent white paper, Samsung Biologics’ Pierre Catignol, executive vice president and head of manufacturing, and Huisub Lim, lead scientist of mRNA manufacturing, explained how important it is for clients seeking a CDMO partner to consider the CDMO’s ability to manufacture mRNA quickly at different scales.

“With base capabilities established, a sponsor’s next concern is process agility and a commitment to speed to market — the criticality of which were increased during the pandemic,” they wrote. “Dedicated manufacturing slot availability, guided by a well-established agreement, is key to that agility. 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).”

Scaling Challenges and mRNA Vaccine Production Solutions

One of the innovations of mRNA vaccine production is that it can overcome scaling challenges that have historically slowed time lines for developing and manufacturing traditional vaccines.

Several factors contribute to the challenge of quickly and efficiently scaling up production of traditional vaccines. A major challenge is the need for large quantities of virus or bacteria to be grown in cell cultures, an often time-consuming and expensive process. It’s also difficult to optimize, as the growth conditions for each virus or bacteria may be unique and require extensive testing to identify the optimal conditions.

Another challenge with scaling up production of traditional vaccines is ensuring consistency and quality control. Each batch of vaccine must be tested to ensure that it meets safety and efficacy standards, and batches may display significant variance. This makes quality control a complex process that can slow production.

MRNA vaccine production can address many of these scaling challenges. The synthetic production process used to create mRNA vaccines does not require the growth of large quantities of virus or bacteria, reducing the time and cost of production and allowing scales to be adjusted as needed. Additionally, the production process can be easily optimized for different viruses or bacteria, as the mRNA molecule can be synthesized quickly and easily.

Catignol and Lim explained that the most easily scalable aspects of mRNA vaccine production are the initial stages.

“Ease of manufacture is applicable only to the in vitro transcription (IVT)

reaction and purification steps of the mRNA production process (not the [lipid nanoparticle] encapsulation). These initial steps are rendered easily scalable due to a synthetic chemical regimen rooted in thermodynamics, which is easy to scale up.”

Quality control is also simplified with mRNA vaccines. The production process is more consistent because it does not require living cells or organisms. This reduces the variability between batches of vaccine and ensures that each dose meets safety and efficacy standards.

And while LNP production can present a challenge, effective LNPs protect mRNA from degradation, improving the stability of vaccines during storage and distribution.

Samsung Biologics has focused on addressing the difficulties in producing LNPs at different scales to meet a variety of mRNA vaccine production needs.

“Samsung Biologics leverages a seamless scale-up system for the LNP

process (i.e., a consolidated LNP process platform, operable from small to large scale),” wrote Catignol and Lim. “The process platform for LNP differs greatly between small-scale developers, who rely mainly on microfluidic mixing, and large-scale manufacturers, who generally use T-mixing systems. Thus, gap analysis is necessary to ensure product consistency when scaling up.”

Scaling With End-to-End Solutions

For Samsung Biologics, the key to taking advantage of the scalability of mRNA vaccine production is providing a one-stop shop with both drug substance and drug product services. By handling all the steps of the process under one roof, Samsung Biologics can scale projects quickly while sidestepping potential supply chain issues and degradation caused in transport.

“Few manufacturers/CDMOs are adequately equipped or capable of carrying out all manufacturing steps, leading to logistical, monetary,

and time line difficulties. Frequent handling of mRNA across multiple locations increases contamination and degradation risks,” explained Catignol and Lim.

“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.”

By Manali

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