Bioprocess control in line using optical sensing

Optimising feed control can improve the yields, quality and cost efficiency of bioprocesses. Stratophase has developed in-line, continuous optical measurement technology that can help.

Within pharmaceutical process development there is a driving need for control and monitoring instrumentation that is robust, easily installed, suitable for all reactor sizes and operator independent. Additionally, the FDA’s Process Analytical Techniques (PAT) and Quality by Design (QbD) initiatives are leading the industry to adopt real-time, continuous monitoring techniques that allow better knowledge from inside the process.

Historically, process control has been a combination of real-time physical data such as pH and dissolved oxygen (DO) and off-line, lab-based, analytical sampling with process quality determined after the process is completed. Figure 1 depicts the number of steps and the time taken with current approaches. Additionally, the absence of real-time, continuous monitoring has restricted the use of fed-batch or continuous nutrient feeding regimes, which allow greater optimisation of both the process metabolic rate and the use of process consumables.

Of particular interest is real-time control of glucose, the nutrient in many bioprocesses. Recent advances in micro-optical sensing technology means that real-time, in-line monitoring of glucose, within the process media, is now a reality. This allows manufacturers to implement a fed-batch strategy using glucose consumption rate, which automates the feeding regime, takes fewer steps and can be repeated frequently. The comparative control loop using real-time monitoring is illustrated in Figure 2. In addition to feed control, this approach provides manufacturers with key process data such as batch-to-batch process monitoring, maximum metabolic rate and end of process, a notoriously difficult parameter to monitor. Each of these additional data points increases process knowledge and influences process yield and quality.