Forging Ahead with Continuous Manufacturing for mRNA (BIO 2024)

The summer of 2023 was a busy time for government investment in messenger RNA (mRNA) manufacturing advances. As part of the Biden administration moonshot initiative, the Advanced Research Projects Agency for Health (ARPA-H) announced the launch of “Curing the Uncurable via RNA-Encoded Immunogene Tuning” (CUREIT) project. This effort, led by a team at Emory University in Atlanta, Ga., with up to $24 million in new funding, has the goal of developing “… generalizable mRNA platforms that can be harnessed to train the immune system to more effectively fight cancer, … other applications could extend to autoimmune disorders, transplants, and infectious diseases” (1). A month prior to the Biden administration’s announcement, Peter Marks, director of the Center for Biologics Evaluation and Research (CBER) at FDA, allocated an award of $82 million to Massachusetts Institute of Technology (MIT) researchers to create a center for continuous mRNA manufacture (2). The main manufacturing subcontractor for this three-year pilot program is ReciBioPharm. The over-arching goal is to establish the first biologic drug using a fully continuous manufacturing integrated process, from in-vitro transciption (IVT) to fill/finish.

At the BIO 2024 conference held in San Diego, Calif., on June 3–6, Pharmaceutical Technology Group’s Chris Spivey spoke with Aaron Cowley, PhD, chief scientific officer at ReciBioPharm to check in on the pilot program’s progress. Cowely stated that “being able to have eyes on the process, and the product, as it goes along the full train of manufacturing, and being able to release that data in real-time, that is the overall goal.” When addressing potential scale-up bottlenecks or other obstacles, particularly on the analytical side, Cowely went on to say, “the beauty of this grant is that we are able to take the best technologies, regardless of company source, and incorporate them, to see what’s working and what’s not work[ing] [for continuos manufacture]. After a year and a half, we already have a process development system that’s capable of going from [IVT] through [to] fill/finish, fully operational, so we’re collecting data. We have the process analytical technology (PAT) that’s actually driving the process already. We can see the kinetics of the process. We can see the impurity profile. We can take the material and send it to waste, if it's not meeting criteria, or move it ahead to the next unit operation … we’ve been using off-the-shelf PAT equipment, but not in the way it’s been traditionally deployed.”

The pilot project has placed a heavy emphasis on process modeling with the help of machine learning to repeatedly evolve the system performance and product outcomes. Cowley said they’ve hit paydirt by now being able to remove system variability and are now “able to control what others currently cannot control. It’s like manufacturing in a vacuum. So, it’s much easier to track your product, and the quality of your product.”

References

1. The White House. As Part of President Biden’s Unity Agenda, Biden Cancer Moonshot Announces Launch of ARPA-H’s CUREIT Project Led by Emory University to Develop New Tools to Strengthen the Immune System and Save Lives. Press Release. Aug. 23, 2023.
2, Winn, Z. MIT Researchers to Lead a New Center for Continuous mRNA Manufacturing. news.mit.edu. July 13, 2023.