In a recent review, Trent Munro, PhD, National Biologics Facility, University of Queensland, Australia, writes that “Improvements in process and cell line development, the advent of single-use technologies, and a dynamic market, have subsequently led to the pursuit of smaller, intensified processes. This change is further reflected in the regulatory landscape where guidance on continuous manufacturing has been issued recently. This includes the implementation of a lot strategy comparable to traditionally favored individual batches.”
In a follow-up interview, GEN asked Munro about specific categories within bioprocessing that might be ripe for continuous/perfusion culture. In other words, perfusion has been around for a long time—where’s the beef?
“‘Dynamic market’ refers to specially products that won’t require 100kg/year but rather a more flexible approach to market supply. The mega blockbuster antibody products are few and far between, while markets for niche, high-value products continue to grow,” he said. “Examples include complex bispecific antibodies, enzyme replacements, or treatments for other rare diseases, all of which are traditionally produced through small batch processes. Moving toward a modern perfusion process might offer advantages in cost of goods and geographic production flexibility. In terms of scale, I could see processes in which the production bioreactor might be only ten to fifty liters.”
Adoption of perfusion (and other innovative production technologies) has previously been limited to new processes, but that could change, according to Munro.
“I think there is a huge opportunity for older bioprocesses to switch to a smaller footprint,” he added. “This would also allow a swap to newer equipment with dramatic potential for improved process robustness and efficiency.
“The elephant in the room is achieving product comparability and the required regulatory submissions that come with a risky, expensive, and time-consuming process change. There is a reason why some products today still use animal component-based culture media or complex roller bottle processes. These challenges also need to be overcome with new regulatory paths and streamlined processes for change.”
But hasn’t perfusion cell culture been around for quite a long time? If continuous cell culture was so great, why doesn’t every CHO process (or even every new CHO process) employ it?
“This is definitely not a one-size-fits-all solution,” Munro tells GEN. “Previous perfusion production was done out of necessity, which was driven by unstable products or low yield processes. Many companies today use complex process modeling that can guide development and manufacturing strategy. Rather than automatically defaulting to a large-scale fed-batch commercial process, we will see molecules being developed with a fit-for-purpose strategy, in terms of both scale and process.
Certain companies are further along this journey, but it takes courage and commitment to embrace new technologies and take some risk along the way. At the end of the day, what matters is: the right process for the right molecule to enable the right type of commercial production. Modern intensified perfusion processes are just one additional strategy in that toolbox.”