Process intensification has become a hot topic in biopharma in recent years, with concepts like continuous manufacturing and “scaling-out” increasingly cited as investment drivers by drug firms and the developers that supply them.

But despite the increased availability of methods and technologies that support higher output, intensification remains a complex and costly undertaking, according to Paul Cashen, PhD, a consultant at Sartorius Stedim Biotech.

“Generally, cost of implementation and deciding what approach is best for their own process can be considered the key challenges,” he says. “There is no one-size-fits-all approach to process and implementation of these methodologies which should be directly linked to the type of improvements that need to be made, such as time savings, facility footprint reduction, or increased productivity.

“Process intensification comes with increased system and technology complexity, necessitating higher upfront CAPEX investment. Therefore, companies need to ensure they are implementing the correct strategy for their process to prevent over-investment in terms of time, money, and labor,” Cashen says.

Strategic process intensification

Intensification strategies should be based on data, says Louis Crowley, PhD, technical manager of separations technology at Sartorius Stedim North America who—with Cashen and colleague Martin Lobedann, PhD, process technology manager at Sartorius Stedim Biotech—analyzed industry efforts to increase output in a recent study.

“The ideal approach begins with modeling. Initially, the focus should be on each step of a process in turn—the level 1 approach—followed by an examination of how those steps connect—which is level 2,” Crowley says.

He cites chromatography as an example, explaining, “The capture step is generally a higher cost step because it involves Protein A, an oligo for mRNA, or even a custom ligand. Within this step, you have multiple options. You may move to sequential multi-column chromatography with a system capable of performing the operation.

“Alternatively, you may move toward membrane chromatography and rapid cycling. Either way, you are concentrating on a single step where you can focus on optimization in line with your process intensification goals. At level 2, in contrast, you are looking at how to optimize the connection between optimized systems,” he says.

For co-author Lobedann, this stepwise approach is key. “Once optimization targets have been identified, these can be realized in a stepwise approach by intensifying single unit operation. Here also process development and characterization need to be included, in case different critical parameters are identified compared to a traditional batch downstream processing,” Lobedann says.

Previous articleDigital Twin Approach Triples Productivity for Lyophilization
Next articleImproving Cell Therapy Supply Chains