How BioPAT^® Supports Cost Savings

The commercial bioprocess market is growing rapidly. However, the economic climate, rise of biosimilars and high cost of R&D are putting pressure on the end cost to the patient. Biomanufacturers are moving to multi-product facilities or outsourcing production, developing a competitive contract manufacturing market. Thus, with these drivers, future processes must have:

• higher space time yields
• faster development cycles
• shorter turnaround times
• lower manufacturing running cost
• lower material wastage
• improved quality documentation

Overall Sartorius Stedim PAT enables the improved monitoring and control of bioprocesses. This is by the accurate analysis of Critical Process Parameters (CPPs), the timely acquisition of key performance indicators, accumulated into a simplified model for easy interoperation. Thus, the result is shorter time to market by faster development cycles as well as assurance of final product quality and process performance. Additionally, the enhanced real-time understanding and control minimizing deviations, waste and time/cost.

Real-time viable cell density process tracking allows you to transfer your cells to the next stage of the process eliminating under/overshooting and sampling. Thus, decreasing batch to batch variability and allowing a tight upstream manufacturing process line schedule.

In commercial biomanufacturing the method to cascade cell growth by reaching a desired cell density and inoculating the larger sized vessel has a strong influence on the overall upstream processing time. If an unknown influence affects the cellular growth rate, this time will fluctuate and generate issues in planning and scheduling a process. Therefore, online tracking of cell density allows the transfer of inoculants precisely at the desired cell density point and gives earlier indication of schedule changes allowing improve process planning. Ultimately, this will minimize the downtime related to downstream transfers and material availability, opening the possibility of just-in-time manufacturing and increased upstream capacity.

A typical CHO cell line process maintains glucose at more than 3 g/L. This allows a safety margin for late feed addition and method. However, it’s understood that overfeeding CHO cells results in higher lactate concentrations, and lower product yields. Additionally, higher end point lactate concentrations creates inefficiencies in downstream process. Thus, an improvement in optimal glucose feed control has a positive impact on productivity, minimize excess production of lactate and reduce cumbersome and labor intensive operator steps.

The solution comes by way of tightly controlled glucose concentration set point in the media. This is achieved by the BioPAT^® Trace utilizing a 2-point or PID control loop maintained by either the local controller or BioPAT^® MFCS. With a rapid, continuous, and accurate measurement of the glucose concentration, this signal is fed through the BioPAT^® DCU controller, and on to BioPAT^® MFCS, which actuates a sophisticated PID control strategy for the feed pump thus maintaining the desired glucose concentration set point.

Many aspects of Biosynthesis have remained manual operations. Historically, this has been due to the absence of robust, real-time measurement methods which are able to provide accurate results for a variety of critical process parameters both at bench and production scale. In a PD or manufacturing setting, manual feeding requires significant resources for offline measurements, calculations and pump adjustments. By applying automation, the benefits are significant, improved throughput, risk avoidance and ultimately cost savings. Additionally, operators can be free to focus on other tasks.