Scale up

Scaling is an important aspect with respect to any cell culture process which involves transferring a bioprocess from one bioreactor size to another which can include scale-up and scale-down. Scale-up is required when a process is being developed for smaller, easy to handle volumes, with the final goal of commercial manufacturing at a much larger scale. Scale-down on the other hand is critical to troubleshoot large scale processes, for producing smaller quantities of product and to verify process condition changes.

When moving from a small scale system to commercial manufacturing, the critical quality attributes of the product being developed and manufactured should be identical. Therefore, it is imperative that the key parameters and performance during the scaling process are kept constant.

As an example of how Aber’s capacitance technology is scalable, Figure 1 and 2 show cultivations in RM 50, RM 200, STR 50, STR 200 and STR 1000 platforms (Sartorius, Germany) using capacitance to monitor biomass. Capacitance trends measured using the single use BioPAT Viamass were observed to be comparable across these platforms, thus indicating successful scale up. This demonstrates that not only can Radio Frequency Impedance measurements be used across platforms, but can also be used to determine the success of the scaling strategy across different platforms.

Figure 1 – Example of cultivations in SSB RMA 50, RM 200, STR 50 and STR 200 platforms using the BioPat Viamass sensor (Data Courtesy of Sartorius, Germany)
Figure 2 – Example of cultivations in SSB STR 50, STR 200 and STR 1000 platforms using the BioPat Viamass sensor (Data Courtesy of Sartorius, Germany)

Summary of the benefits

  • Use the technology across different platforms and scales successfully
  • Key performance indicator for scale-up success
  • Monitor cells in situ and in real time in a variety of bioreactor platforms (reusable and single use)
  • Eliminates/reduces need for sampling
  • Perform cell density measurements non-disruptively
  • Obtain fingerprint of the process in real time
  • Can be used to measure a variety of processes – batch, fed batch, perfusion, continuous processes
  • Troubleshoot the process
  • Control critical events during the process
  • Automatic cell concentration control
  • Automatic complex nutrient feed control
  • Improve productivity and process consistency