Monoclonal antibody makers should consider swapping batch for continuous production, according to research suggesting new tech has made switching less of a risky endeavor. The study looked at the benefits of converting downstream processes and found that if done properly, swapping to continuous mode has a positive impact on output, time to market, and profitability.
The team used two unit operations–protein A capture chromatography and ultrafiltration—as models and found that continuous mode achieved a 28% productivity improvement. In addition, total process time was cut from four days to less than 24 hours.
The findings are apposite, according to lead author Ran Chen, PhD, head of downstream process development at Shanghai Henlius Biotech, who says industry interest in intensified production for established products is increasing.
“Market demand for the products made using batch processes is certain, which means low risk,” says Chen. “Under such circumstances if a batch process is converted into a continuous process, capacity can be greatly increased, and the cost can be reduced with the same line.”
Analytical changes
But mAb manufacturers that do switch will need to become comfortable with novel methods and technologies, continues Chen, citing predictive modeling as an example.
“In batch processes, usually offline analytical testing is used, and process models are rarely employed, while in continuous processes, online analytical testing and modeling are essential for several key reasons,” he explains. “Continuous processes are usually more complex than batch processes, which include a larger number of process parameters. Process modeling can help to facilitate development and reduce the experimental workload in continuous process development.
“Secondly, the production cannot stop and wait for the test results before proceeding to the next step, and the residence time distribution (RTD) of material within the whole process needs to be determined. Therefore, online process analytical technology (PAT) combined with a model is also important in continuous process.”
Invest upfront
In addition, companies moving to a continuous model will need to think about operations on the factory floor as, obviously, any process running 24-7 cannot be overseen by a single operator or shift team. Instead, drug companies will need to invest in technologies that monitor production and provide real-time information to the operations shift working at the time.
Fortunately, such systems are available. However, mAb firms will need to plan their implementation carefully, emphasizes Chen.
“Most biopharma firms could convert from batch to continuous mode. However, there must be a well-built automation platform, such as Emerson’s DeltaV system, set up ahead of time,” says Chen. “Any monitoring system will need on-line detection capabilities for pH, conductivity, and other key parameters. Besides, you may still need to replace or add some necessary equipment, for example, MCC equipment, ILC, ILDF device and surge tanks etc.”
