The benefits of continuous manufacturing a clear: increased output at lower cost with less waste. At least on paper, but 24/7 production can be a challenge for traditional drug firms says the team behind a new digital mAb processing method.
Controlling a biopharmaceutical continuous process is a conceptual shift for an industry built on batch-mode manufacturing according to Anurag Rathore, PhD, from the department of chemical engineering, Indian Institute of Technology in Delhi.
“Continuous manufacturing integrates multiple unit operations and the risk of product or process deviations in this set up necessitates use of robust and intelligent controllers that are capable of handling them in an automated manner,” according to Rathore.
To that end, Rathore and colleagues developed a “cyber-physical” production system (CPPS) they describe as a framework where physical processes are integrated with digital tech to enable real-time monitoring, control, and optimization.
“The CPPS represents a significant evolution in manufacturing, enabling Industry 4.0 principles by transforming traditional factories into smart, interconnected environments capable of autonomous decision-making and adaptive manufacturing strategies,” he told GEN, adding that the ability to monitor process parameters in real-time will be welcomed by monoclonal antibody manufacturers.
“This type of real-time monitoring allows for proactive identification of deviations, reduced downtime, and optimized production schedules compared to the reactive approach in conventional manufacturing,” continued Rathore, who also cited the ability to adapt output in line with demand as a key feature, explaining manufacturers “can quickly adjust production parameters, switch between product variants, and accommodate customizations without significant retooling or downtime.”
Implementation
The CPPS combines three modules: an integration system designed to help manufacturers link bioprocessing technologies from different suppliers; a data management unit that collects and processes readings taken from each unit operation; and a control block.
“For integration various strategies are available. One option is to use programmable logic controllers (PLC) over a local intranet to facilitate the scheduling of the different steps in the manufacturing process with linked triggers,” noted Rathore.
For data management, the study authors use a system that combines real time analytics, historical data, pre-processing algorithms and visualization software to gives engineers instant process feedback.
“The system also has the data stream buffering component, which has the ability to handle large volumes of data from all the equipment and sensors simultaneously, with high frequency, passing the data onwards to the next component without undue delays,” explained Rathore. “The next component is data processing, where the data are analyzed and trended using various algorithms including statistical upper and lower limit detection.”
The third element of the CPPS is a “responsiveness model” that has overall control of the process. It has a “knowledge management” component, which brings all process data into one context for control and contains strategies that can be executed in response to analytics, including digital twins and surge tank- based control strategies.
The aim was to develop a universal platform for the monoclonal antibody industry, stated Rathore, adding that “Any manufacturer trying to set up a continuous mAb production line should consider the proposed framework.”
