Research recently published in Current Opinion in Chemical Engineering looked at challenges industry encounters when switching from batch to continuous-mode processes for mAb therapeutics and found that effective control is a major hurdle.

Author Anurag Rathore, PhD, from the DBT Center of Excellence for Biopharmaceutical Technology at the Indian Institute of Technology in Delhi, says industry finds it difficult to move continuous processes from lab to commercial scale.

“Continuous processing has been garnering much interest lately for production of biopharmaceutical products. Purported benefits include higher productivity, often 10–15X, significant shrinkage in facility footprint as well as equipment cost, and improved process control and consistency in product quality,” Rathore tells GEN.

“However, industrial implementation remains a non-trivial task due to the significant complexities associated with controlling continuous processes. Real-time monitoring of critical quality attributes followed by real-time process control while desired, may not be feasible for every attribute and for every unit operation.”

Real-time analysis

Even in a batch process a typical monoclonal antibody therapeutic has a large number of critical quality attributes that need to be measured.

In a continuous mode production these same attributes need to be measured in real time for as long as the process runs, which requires a very different approach, Rathore says, citing glycosylation as an example.

“Analysis of glycosylation pattern of a monoclonal antibody product requires a series of complex steps including enzymatic digestion, HPLC, and mass spectrometry,” continues Rathore. “The additional burden that comes in continuous processing is the significant reduction in time that the manufacturer has to take a decision.

“Batch production, though inefficient, gives the manufacturer the luxury of performing analysis and deciding on the future course of action.”

Innovative solutions

Going forward, real-time monitoring will become less of a challenge, according to Rathore, who predicted recent advances in analysis technology will ease the implementation process.

“The past few years have seen major developments in analyzers, particularly spectroscopy for real-time monitoring, process modeling—both mechanistic and empirical—as well as use of advanced data analytics to tie it all together,” notes Rathore. This combination is emerging as the future for manufacturing 4.0.”

Ultimately, any mAb maker that wishes to use continuous processes needs to use innovative analysis technologies as part of a robust and adaptable automated control system, Rathore says, stressing that “to effectively control a continuous process we need a combination of an appropriate analyzer or sensor, process model, and data analytics.

“This combination can be effectively used for facilitating real-time process monitoring and real-time process control. Artificial Intelligence is already being used heavily in drug discovery and gradually making its way into bioprocess control. As per my knowledge, all major drug companies are working towards creating their own flavor of process control,” Rathore explains.