In a recent article in the Journal of Chromatography A, lead authors Alexander Armstrong, Stephen Goldrick, PhD, and Kieran Horry, of University College London, write that “novel control strategies [that] combine rapid in-line data capture (e.g. NIR, MALS, and variable pathlength UV) with enhanced process understanding obtained from mechanistic and empirical modeling,” could help to overcome the shortcomings of existing monitoring and control methods.

In an interview with GEN, Armstrong noted that “continuous chromatography control systems are more advanced due to the added operational complexity resulting from the use of multiple chromatography columns. These control systems require an additional column switching controller to maximize binding capacity and optimize column switch times.”

Although sensing and controls are more advanced, and more widely deployed, in batch vs. continuous processing, these modalities are interchangeable between batch and continuous. “The control of batch processes is better understood and characterized and is the most common mode of operation. However, continuous processing offers the potential of higher yields and better economics, but we need to build more confidence in its benefits before industry fully adopts this mode of operation,” said Goldrick.

Adopting advanced sensing and controls, which are essential components of Biopharma 4.0, will likely occur in continuous processing first for downstream unit operations like membrane filtration and chromatography, as these are less complex than upstream unit operations and also involve fewer variables to control. .

“The most critical unmet need for control for both upstream and downstream is a lack of robust real-time process monitoring systems to inform the control unit. However, great progress is being made here, especially for chromatography as we highlight in the paper. Greater accessibility to chromatography mechanistic modeling software, and the recent applications of multivariate data analysis to spectroscopy in academia, are showing real promise for advanced control,” explained Horry.

As always, the question is not whether biomanufacturers and their suppliers can solve the engineering issues holding up adoption of continuous processing, but whether solving those problems will make a difference in terms of adopting continuous processing.

Here Horry and Goldrick believe that “advances in process monitoring and control will further enable the transition from batch to continuous biologic manufacturing. Advanced process modeling can simplify the process design and development of the more complex continuous control systems, and real-time monitoring of the process will better inform column switching and pooling controls.”