Implement Creative And Collaborative Strategies to Optimize Your mRNA Development And Manufacture
By Life Science Connect Editorial Staff
The landmark application of mRNA vaccines to treat the COVID-19 pandemic led many drug developers to begin exploring the therapeutic possibilities of mRNA, which is now being leveraged to design vaccines, protein replacement therapies, cell therapies, and gene editing therapies. However, to successfully deliver powerful mRNA drugs to patients, drug developers will need to enlist the support of knowledgeable and experienced partners, including contract development and manufacturing organizations (CDMOs). As more CDMOs enter the mRNA market, sponsors must thoroughly vet potential manufacturers to ensure they have the capabilities to successfully produce these next-generation therapies.
In your search for an outsourcing partner, it is critical to consider whether a CDMO can achieve your quality goals while staying within budget and maintaining your timeline. Below, we break down the key factors you must assess when evaluating a potential CDMO’s technical and platform capabilities.
What Is The Current State Of mRNA Outsourcing?
Historically, many CDMOs strived to be one-stop shops that promised to fulfill the needs of any project for which a drug company sought support. Now, as innovator companies identify their specific lanes of mRNA therapy development, CDMOs are considering whether the one-stop-shop model will be the best strategy in today’s increasingly complex and competitive market. According to the Founder of Aust Business Solutions, Alexander Aust, CDMOs are asking, “What are we good at? Where do we want to focus? Are we overclaiming what we are doing? Are we actually a CDO [contract development organization]?” Luckily, there is room for all types of partners in the burgeoning mRNA space.
At this still-nascent stage in the industry, an outsourcing partner’s capabilities may only be suited for certain phases of development. For instance, a Phase 1 project has different support criteria than a commercial stage product, which requires quality process validation and regulatory support. mRNA CDOs are emerging to assist with the development stages, and a wide range of global companies now produce different types of lipid nanoparticles (LNPs) with data to support their quality and effectiveness. CDO teams collaborate with pharma companies during development stages before handing a project off to CDMOs with GMP capabilities. Some sponsors opt to conduct their development work in house, only seeking a manufacturing partner when they are ready for the GMP stage.
In an ideal world, all stages of mRNA development and manufacturing could be completed under one roof. However, the wide array of technologies and capabilities needed will likely require several different vendors. Consider the technologies required to manufacture plasmid DNA or conduct CRISPR gene editing, lyophilization, and aseptic fill-finish. Having all these offerings under one roof is resource-intensive for one CDMO, and, as such, mRNA developers should be prepared to work across multiple partners for different development stages and/or production needs.
As they determine which stage of mRNA manufacturing they are best prepared to accommodate, CDOs and CDMOs are also exploring how cutting-edge technology can yield more efficient and cost-effective processes. Prior to the COVID-19 pandemic, CDMOs were primarily focused on manufacturing linear mRNA; now, many have expanded their focus to optimizing each template. This has led to the increased application of automation, innovative approaches within the in vitro transcription (IVT) process, and the implementation of flow chemistry to produce and harvest mRNA rapidly while allowing for better stability and improved yield.
CDMOs and developers are considering where and how AI can be used to establish efficiencies throughout their workflows. From a manufacturing perspective, AI can be used during the GMP phase to demonstrate data trends and predictions that help manufacturers derisk and strategize. Overall, a growing number of mRNA CDMOs and new technologies are helping to create more competitive pricing options for mRNA sponsors.
What Should You Look For In An mRNA CDMO?
When selecting a CDMO to manufacture your mRNA product, one of the important distinctions to make is which clinical phases a vendor can best accommodate and whether that skillset aligns with your needs. Phase 1, 2, and 3 each have different scale, regulatory, and quality requirements. Ruan notes that which phase a CDMO can accommodate is perhaps even more important than their previous experience with a specific type of mRNA, adding that: “[For self-amplifying mRNA], we try to use similar or the same equipment to [conventional mRNA] manufacturing. That way, when we do the CDMO evaluation, if they can make conventional mRNA, there is a strong possibility that they can make self-amplifying mRNA.”
The drug sponsor and CDMO relationship relies heavily on transparency and collaboration. In your search for a CDMO that will successfully manufacture your mRNA therapeutic, prioritize finding a partner that is willing to collaborate with your team to craft solutions and commit the necessary resources to problem solving. Leverage your site visit to ensure that your project will be overseen by an experienced and dedicated group.
Andrew Geall, Chief Development Officer and Co-Founder of Replicate, recommends the following approach: “When you do a site visit, walk around. Talk to the people. Try to understand how many teams they have and who you would be working with. What is their background and experience? Typically, with new technologies, stuff happens. You want a team that raises a flag when there is a problem and says, let’s fix this.”
Beyond a willingness to address issues head on, you want to identify a CDMO that has experience navigating global regulatory requirements on tight timelines. Their team should offer robust documentation practices to help support your regulatory filings.
For Ruan, selecting the right CDMO comes down to asking a few specific but critical questions: “If they say that they can make your product, can they really? Do they have experience with similar products? Is their facility fit for their purpose or is there flexibility?” These projects are complex, and to succeed, the sponsor and CDMO will need to work together collaboratively to check off the necessary goals to maintain quality and compliance.
What’s The Bottom Line?
No matter how you approach it, mRNA manufacturing is expensive, from early-stage development to running GMP processes. The raw materials, technologies, and educated labor force required to manufacture mRNA simply require immense investment. To avoid incurring extra costs and to ensure your strategy is precise and risk averse, identify an experienced partner that prioritizes transparency, communication, and first-time-right manufacturing.
The content of this article originally appeared in a live event for Advancing RNA.