A three-year research program led by faculty at MIT aims to design the world’s first fully integrated, continuous mRNA manufacturing platform, in an $82 million effort funded by the U.S. Food and Drug Administration (FDA) Center for Biologics Evaluation and Research.
The resulting pilot-scale system is intended to improve society’s ability to respond to future pandemics as well as accelerate the development and production of mRNA technologies, which companies are investing in at unprecedented scales in hopes of developing new vaccines as well as new treatments to cancers, metabolic disorders, genetic diseases, and more.
“All of these companies are investing hundreds of millions of dollars into mRNA, not because of Covid, but because of mRNA’s future potential in all these other disease areas,” says Richard Braatz, the Edwin R. Gilliland Professor in MIT’s Department of Chemical Engineering and the principal investigator for the project. “If we can drive the cost and time of development down, we’ll enable all sorts of new applications.”
The engineering challenges will be tackled by researchers at MIT as well as collaborators at Penn State University, led by Professor Andrew Zydney, and Rensselaer Polytechnic Institute, led by professors Steven Cramer and Todd Przybycien. A substantial portion of the project has been subcontracted to ReciBioPharm to implement the end-to-end process developed by the researchers in a pilot-scale manufacturing facility.
The main goal of the project is to advance the field of mRNA therapeutics by providing a continuous manufacturing template for companies to follow, while facilitating collaboration throughout the biopharmaceuticals industry. The research team will also work closely with the FDA to ensure the pilot-scale system adheres to current good manufacturing practices and informs regulatory strategies. All of this helps significantly de-risk the development of mRNA technology.
“This project has public health significance because a continuous mRNA manufacturing platform has the potential to serve as an adaptable, agile tool to address emerging health threats both in the United States and globally,” says Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research.
Messenger RNA, or mRNA, carries instructions that cells use to make proteins. Scientists have studied mRNA for decades, but its use to develop successful Covid-19 vaccines has supercharged development of the technology.
Like the production of many other biologics, the current production of mRNA is batched and requires many steps that create bottlenecks in its production. Continuous manufacturing, in contrast, allows a product to be made non-stop and avoids delays caused by pauses and transfers between batches. Researchers involved in the new effort explain that integrated and continuous manufacturing processes have been shown to reduce the time to market of new drugs, ensure a modular and flexible supply chain, and reduce costs. Continuous manufacturing should also improve the quality of mRNA production through automation and in-line analytics, Braatz notes.
Those features will help meet the booming demand for mRNA material and make it easier to ramp up production of new mRNA vaccines quickly in the event of a pandemic or other public health emergency.
“What you really want to do is prepare for the next pandemic, not the last one,” says Braatz. “You want to nip it in the bud quickly by developing a vaccine the moment the virus is spotted. The current technology is too slow to get ahead of pandemics, but if we can develop these technologies further, that might be possible.”
The FDA will disburse the funds to MIT over a three-year period. A significant portion of the project has been subcontracted to ReciBioPharm as it builds the manufacturing facility. Work at MIT is already underway to develop automation and advanced controls for quality assurance and improve midstream processing.
“Continuous manufacturing of mRNA therapeutics has vast potential; the value of being able to quickly and safely create targeted mRNA treatments for known and not-yet-known threats is immeasurable,” says Paula T. Hammond, MIT Institute Professor and head of the Department of Chemical Engineering. “This project is an excellent example of how chemical engineers can help to address significant needs in making the medicines of the future. The MIT Department of Chemical Engineering is proud to help facilitate this exciting project. We look forward to collaborating with the FDA and fellow researchers to make this ambitious goal a reality.”
This new research program builds on the success of the Novartis-MIT Center for Continuous Manufacturing, a $85 million program that ran from 2007 to 2019. The Novartis-MIT program developed and demonstrated the world’s first bench-scale integrated continuous manufacturing system.
“All large-scale chemical production is done continuously,” says Allan Myerson, a professor of the practice at MIT and a co-PI of the new award. “Pharmaceuticals have traditionally not been continuous, but for the last 15 years or so there’s been a lot of work to move toward continuous at places like the Novartis-MIT Center for Continuous Manufacturing, and in my experience the FDA has been very supportive of this because of not only the increased efficiency but also the fact that you’re operating at steady states, [which] allows you to optimize conditions and make a high-quality product at all times.”