TECHNOLOGY AND INNOVATION
equipment. The CDMO plans to grow its use of CFM in its site while announcing expanded batch capabilities. But while CFM may have received renewed
attention, obtaining funding remains challenging, says Vikramaditya Yadav, associate professor at the Department of Chemical & Biological Engineering at the University of British Columbia. Some companies are careful while investing in it while waiting for more assurance instead, Yadav explains. The scale of the move toward continuous manufacturing could also depend on existing investments, says Hartman. Companies that developed facilities featuring semi-batch to improve what they already have, rather than buying anew, he adds. To be worth the investment, continuous processes would need to replace batch procedures that were made for assets designed with batch manufacturing in mind, says Kappe. This careful approach holds the sector back to an extent, he adds.
Investing in different methods Companies also remain afraid of investing too much capital into developing continuous manufacturing protocols for assets that may eventually fail in the clinic, adds Kappe. They could, however, focus on manufacturing generic drugs that are always in high demand using continuous flow methods, he says. Yet the production of generics and critical medicines is not as attractive to venture capitalists as it would be for high-value compounds, says Thompson. He describes this as somewhat of a “Catch-22” situation, where governments became interested in CFM as a means of securing a molecule that was in shortage during the pandemic, but such lucrative to potential investors, he explains. And while some have successfully adapted CFM practices in downstream processing, upstream processing appears as a potential risk to venture capitalists, Thompson says. In addition, securing talent has also proven people trained with the understanding of continuous processes, he says. CFM requires a different approach to doing chemistry, with a different skillset, says Baxendale.
28 | Clinical Trial Supply Handbook
New regulations important for greater implementation Although the FDA has approved several continuous processes in the past few years, adapting the current regulatory language remains a work in progress, says Thompson. Regulatory uncertainty acts as a disincentive for investors, he adds. Rather than a challenge, the development of CFM processes can be compared to a certain unknown, where each process and research are distinct and novel, says Baxendale.
The application of continuous processes for biologics production has its own set of challenges, whether it is potential fouling, macro molecules, or even contamination, compared to small molecules, says Hartman. Similarly, the creation of a continuous fermentation process in biopharmaceuticals remains a grand challenge when understanding says Yadav. Still, he says contamination in continuous manufacturing could be easier to control, as it allows the producer to quickly get rid of the issue, but adequate monitoring remains critical. Similarly, CFM of highly advanced therapies such as CAR-T therapy is still at an early stage as their manufacturing remains highly manual, says Jason Foster, CEO of Ori Biotech, a company focused on cell and gene therapy. At the same time, Foster says that CFM could be an avenue to scaling viral vector production.
A gradual flow towards industry As of now, Baxendale says that some aspects of CFM are appearing in the pharmaceutical industry rather than a wholesale transfer to flow chemistry. New tools and processes still need to be created, and many companies consider CFM at a proof-of-principle stage, says Baxendale. Although CFM could play an increasingly visible role in the industry, Kappe anticipates seeing both batch manufacturing and CFM in a hybrid system in years to come. New legislation and regulation could be
key for implementing CFM protocols that sustainability, says Hartman. According to him, without legislative drivers, the question to switch to a new protocol will be driven by
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