Although RNA-based therapeutics are still a relatively new class of medicines, scientists have been studying the clinical use of ribonucleic acid (RNA) for years. Beyond messenger RNA (mRNA), other categories of RNA-based therapeutics have long been established and approved for use, including antisense oligonucleotides (ASO), RNA interference (RNAi) and RNA aptamers. However, the success of using mRNA-based vaccines for Covid-19 spurred public awareness about mRNA’s disruptive potential in medicine.
Today, biopharmaceutical companies of varying size are exploring the development of mRNA vaccines and therapies for multiple indications ranging from cancers like pancreatic cancer to metabolic diseases like diabetes. For example, one company is making progress with an mRNA vaccine to potentially prevent the recurrence of melanoma. Over the next decade, with the spotlight on mRNA, this field is expected to grow exponentially.
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To meet growing demand and successfully bring new mRNA-based vaccines and therapeutics to market, it will be imperative that developers and manufacturers implement the following best practices.
Plan to scale by selecting the right raw materials
Selecting the appropriate raw materials is one of the first and most critical steps in the development of mRNA therapeutics. Ensuring this part of the process is “right” can be a make-or-break moment for the success of a project. Many developers might feel the pressure to preserve funds by selecting materials based on cost. This can be a mistake. Trying to recoup costs upfront by beginning drug development with materials not optimized to the needs of your project can impact long-term success.
For example, choosing a material with limited scalability can cause delays in the manufacturing process further down the line, and even prevent your project from being able to scale to meet market demand. In turn, this can impact future investment opportunities given a lack of ability to scale commercially.
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All of the approximately 150 mRNA molecules currently in some stage of clinical trials have required process development and scale-up, with scale dependent on their target indication.
Consider key questions to ask when evaluating materials and their suppliers, particularly those related to scalability:
- Does the supplier have a proven track record of partnering with drug developers through the commercial launch of new therapies?
- Do they offer product quality assurance, or technical partnership?
As seen over the last few years, it’s also particularly important to understand if a supplier has a contingency plan in case of supply chain challenges and delays.
Establish robust processes to achieve consistency
Vaccines play an integral role in safeguarding human health. However, the process to develop traditional vaccines is significantly more time-consuming than with mRNA vaccines. Historically, it has taken between 10 to 20 years to develop a safe, effective vaccine using traditional technologies. The use of cells and even eggs to produce a traditional vaccine makes them costly to develop too.
In contrast, mRNA-based vaccines for Covid-19 were developed in less than a year. These vaccines are produced biosynthetically without weakened or inactivated viruses, making their development much faster and more cost-effective. They can also be developed and manufactured using a platform process. Another key differentiator is that mRNA vaccines allow for easier analytical characterization, meaning it is possible to characterize both the materials used and the end product itself. This enables a quality by design (QbD) approach to support the consistent and safe development of mRNA vaccines.
A QbD approach identifies and characterizes critical process parameters (CPPs) and critical quality attributes (CQAs) early on to help demonstrate process and product consistency to regulators. Having these parameters in mind beforehand can also help in selecting raw materials based on quality control. Any inconsistencies or impurities present in the raw materials used in a project will need to be accounted for or purified later on, so it’s best to select the materials that will help achieve consistency goals. It’s worth noting that even products said to be “GMP-grade” can vary substantially in quality between suppliers. Pursuing raw materials that are made using validated processes can guarantee lot-to-lot consistency.
Connect with partners earlier rather than later
As mRNA technology and manufacturing processes are still new, “going it alone” with mRNA vaccine or therapeutic development might not be the most opportune path. During the height of the Covid-19 pandemic, the world saw firsthand the power of partnership when it came to bringing mRNA vaccines to commercialization at scale. Smaller companies with less experience bringing vaccines to market partnered with large pharmaceutical companies, while other vaccine developers enlisted the help of CDMOs to help deliver vaccines to more people given their expertise in specific areas like manufacturing and formulation.
The industry is gaining extensive experience with mRNA, but leveraging this technology to its full potential relies on knowledge sharing. Filling in any gaps in an organization’s expertise by collaborating early with partners can help avoid potential roadblocks later in the process. Choosing a partner with solutions that work across the entire mRNA workflow can also help in achieving the goal of consistency and reducing development risks.
The Covid-19 pandemic demonstrated the potential of mRNA on a global stage, as well as the clear benefits of collaboration between developers and manufacturers. The next era for mRNA-based therapeutics and vaccines is here, and it’s time to move from an R&D mindset to a focus on long-term success with mRNA and bringing these innovative therapeutics to patients at scale.
Photo:libre de droit, Getty Images
Dale Patterson, Ph.D. is Vice President and General Manager of Molecular Biology and Nucleic Acid Therapeutics at Thermo Fisher Scientific. When Covid-19 emerged, the Nucleic Acid Therapeutics team partnered with the leading players developing mRNA vaccines, innovated to meet the challenge and scaled its GMP manufacturing of enzymes and nucleotides – delivering more than 9 billion doses of raw materials in support of the companies who helped bring an end to the pandemic.
Dale started his career at Thermo Fisher in research and development and over the last 29 years, has held various leadership positions across product management, service and support and commercial. He spent 6 years living in the Asia Pacific region serving the needs of customers in developed and emerging markets.
