Thu. Jul 25th, 2024

MRNA vaccine production is in the midst of a revolutionary transition to large-scale adoption. As manufacturers expand their capabilities to produce mRNA vaccines efficiently and at a variety of scales, we should begin to see the fruits of decades of research into therapeutic applications of mRNA, including lifesaving treatments for cancer and infectious diseases. This research has already helped stave off the global COVID-19 pandemic.

But the future of mRNA vaccine production will rely on advancements in existing technologies to support a sustainable evolution into new applications. One of these key technologies, say scientists at contract development and manufacturing organization (CDMO) Samsung Biologics, is cold chain storage, which is required to stabilize mRNA molecules throughout the vaccine production process.

In a recent article for Pharmaceutical Manufacturing and Packing Sourcer, Lee Seung-heon, a product logistics specialist at Samsung Biologics, explained how CDMOs had to adapt cold chain infrastructure to respond to the pandemic, writing that those adaptations will be crucial to supporting mRNA vaccine production in the future.

“MRNA vaccines are stored in their solid form and have to be maintained at ultra-low temperatures to avoid the degradation that occurs in non-frozen conditions,” Seung-heon wrote. “This change from the storage of traditional vaccines, which are stable when under non-frozen conditions, provided challenges for CDMOs.

“Although maintaining such low temperatures and tightly controlled cold chain systems was difficult, many CDMOs quickly addressed the issues, implementing cold chain infrastructure to support mRNA vaccine manufacturing and other biologics that need similar temperature control.”

What Is Cold Chain Storage?

Cold chain storage is a system of storing and transporting temperature-sensitive items, such as vaccines, blood products, and other biopharmaceuticals, at a controlled temperature. The use of cold chain storage is critical in the biopharmaceutical industry to ensure the efficacy and safety of these commodities.

In the case of mRNA vaccine production, ultra-cold temperatures are required to ensure the integrity and potency of the vaccine. For example, the Pfizer-BioNTech COVID-19 vaccine needs to be stored at minus 70 degrees C, while the Moderna vaccine requires a storage temperature of minus 20 degrees C. MRNA molecules can quickly degrade if exposed to higher temperatures, so they require continuous ultra-cold storage and transportation conditions.

To achieve and maintain these temperatures, the vaccines are typically shipped and stored in specialized containers that use dry ice or liquid nitrogen as a cooling agent. The process needs specialized equipment and handling procedures and poses unique challenges, but as Seung-heon explains, these challenges can be met by experienced and agile CDMOs.

Seung-heon noted several issues that had to be addressed during the pandemic, including developing primary packaging for a new drug modality and maintaining ultra-cold temperatures in transit. For example, mRNA COVID-19 vaccines were stored in glass vials, but these vials needed to be developed to withstand temperatures that could typically crack glass.

“At these ultra-low temperatures, there is a heightened risk of glass breakage. Thus, destabilizing effects could occur during freezing, and changes in the physical structure of the frozen cap can allow cross-contamination,” explained Seung-heon. “Research into this before the pandemic meant safer vials were developed, and specialist knowledge of processes and solutions was established.”

Other innovations cited by Seung-heon include determining the optimal way to organize vials cooled with liquid nitrogen within a box, and managing the impact of ambient temperature and convection created when vials are placed on dry ice.

The Future of mRNA Vaccine Production: End-to-End Solutions

Samsung Biologics was able to address these and other issues as a manufacturing partner for Moderna’s COVID-19 vaccines. The experience has led the CDMO to build an expertise and expand its mRNA vaccine production capabilities. These capabilities will be crucial as mRNA technology develops to apply to non-COVID applications.

The CDMO expanded its capabilities, which had focused on drug product services such as fill/finishing vaccines, to encompass end-to-end solutions. Samsung Biologics can now produce the mRNA drug substance required for vaccines, then package and store them with its cold chain equipment, all at a single facility. This one-stop-shop approach reduces the risk of contamination caused by transporting mRNA throughout the mRNA vaccine production process.

Cold chain temperatures can be challenging to maintain in transit, and reducing the amount of transportation involved allows Samsung Biologics to avoid this challenge at critical points, then focus its cold chain resources and expertise on only the necessary transportation. This approach also reduces the environmental footprint of cold chain storage.

As the industry invests in developing mRNA vaccines for applications including HIV, heart disease, and cancer, Samsung Biologics’ end-to-end approach could establish the CDMO as a go-to partner for developers working in the mRNA space.

“Although meeting the demands of packaging and cold chain logistics for biologics has been a challenge, it is within the capabilities of CDMOs that have the necessary expertise and facilities,” Seung-heon wrote. “Attention to detail, compliance and keeping ahead of the latest advances are the qualities needed in an external outsourcing partner. Thanks in part to the mRNA vaccine response, the biologics industry is thriving and CDMOs are playing a key role in that success.”

By Manali