MRNA vaccine production continues to evolve, and scientists and biopharmaceutical industry leaders are increasingly optimistic about the potential of this new technology. Researchers are working to build on the success of mRNA vaccines during the COVID-19 pandemic and extend applications of the technology to additional areas, including other infectious diseases, cancer, autoimmune conditions, and genetic disorders.

But despite this promising upside, challenges remain, and the industry is also working to build on the experience gained during the pandemic to improve mRNA vaccine production processes. Contract development and manufacturing organization (CDMO) Samsung Biologics’ solution was to expand its mRNA capabilities in 2022, installing an end-to-end drug substance and drug product facility. The goal was to offer partners a one-stop-shop solution capable of sequencing and synthesizing mRNA, encapsulating the molecules with lipid nanoparticles, then packaging it in vials using a sterile fill/finish process. The process also involves maintaining ultra-cold chain storage conditions as low as minus 70 degrees Celsius.

“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,” wrote Samsung Biologics’ Pierre Catignol, Eexecutive Vvice Ppresident and Hhead of manufacturing, and Huisub Lim, lead scientist of mRNA manufacturing, in a recent white paper.

Samsung Biologics believes its unified approach will help establish it as a leading manufacturing and development partner for the next wave of innovative mRNA projects. The technology is evolving rapidly, and solving production challenges will be a key to ensuring that new technologies reach the public as quickly and safely as possible.

Benefits of mRNA Vaccine Production

One of the crucial advantages of mRNA vaccine production is its remarkable speed. Unlike traditional vaccines, which require time-consuming and complex processes such as growing the virus in cells, mRNA vaccines can be rapidly designed and manufactured once the genetic sequence of the target pathogen is known. This speed allows for a swift response to emerging infectious diseases, as demonstrated by the successful development of mRNA COVID-19 vaccines in record time.

While mRNA vaccines have garnered significant attention due to their role in combating the COVID-19 pandemic, their potential applications extend far beyond this single virus. The versatility of mRNA platforms could allow for the rapid development of vaccines against various infectious diseases, including influenza, Zika virus, Ebola, HIV, and more. Ongoing research is also exploring the potential of mRNA vaccines in providing targeted responses to noninfectious diseases such as cancer and autoimmune disorders.

MRNA vaccines show great promise in inducing potent, precisely targeted immune responses. By encoding the instructions to produce specific viral or pathogen antigens, the vaccines stimulate the immune system to generate a targeted immune response against the desired target. This targeted approach can potentially lead to higher efficacy rates and improved protection against specific pathogens and cancers.

Artificial intelligence algorithms can analyze vast amounts of genetic and protein data to identify potential vaccine targets, predict their antigenicity, and optimize their immunogenicity. This computational approach expedites the discovery and selection of ideal target antigens for inclusion in mRNA vaccines, leading to more effective and tailored immunization strategies.

Challenges in Optimizing Processes

This array of benefits, along with the demonstrated success of the first round of mRNA vaccines during the pandemic, warrants continued research and development into the technology. But, as Catignol and Lim note, CDMOs need to rapidly evolve their capabilities to keep up with this scientific advancement and ensure efficient mRNA vaccine production at a variety of scales.

“Production of mRNA therapies and vaccines involves a complex process that starts with pDNA manufacture and concludes with the fill/finish of formulated products using some type of delivery technology. With commercial scale manufacture of mRNA vaccines underway for just a little more than one year, there are unsurprisingly few CDMOs with extensive expertise in this field,” they wrote.

One challenge associated with mRNA vaccines is their temperature sensitivity. They require ultra-cold storage conditions, which can pose logistical challenges, especially in resource-limited settings. In addition, mRNA vaccines utilize lipid nanoparticles to protect the fragile mRNA molecules and enhance their delivery to cells. The efficient encapsulation of mRNA within LNPs is a novel technique and researchers are actively working on optimizing LNP formulations.

The purification process for mRNA vaccines must ensure the removal of impurities, such as residual nucleotides or contaminants, to meet stringent quality and safety requirements. Additionally, the fill/finish step, where vaccines are packaged into vials, must be optimized for efficiency, scalability, and product integrity. Catignol and Lim noted that Samsung Biologics was able to provide aseptic fill/finish services for Moderna’s COVID-19 vaccine.

“Samsung Biologics is one of the few CDMOs with actual commercial mRNA production experience, as we provided fill/finish services for Moderna’s COVID-19 mRNA vaccine product, including all of the accompanying analytical development and testing for product release.”

MRNA and the Future of Medicine

MRNA vaccines’ capacity for rapid development and targeted immune response offers unprecedented opportunities for global health. The future of mRNA vaccines holds tremendous promise, and ongoing research and development will continue to unlock their full potential in revolutionizing medicine.

By Manali