PSAIChE Biotech: Optimize Flocculation With Real Time Particle Characterization

Since the Seattle area is well known for biotech, I was not surprised when the November Puget Sound American Institute of Chemical Engineers (AIChE) meeting focused on the cell fermentation process at Amgen.   The AIChE meeting featured the presentation by Amgen’s Anna Senczuk:  Particle distribution and cholesterol level as predictors of cell culture flocculation and filterability performance.

With the advancement of cell fermentation technology in recent years, most cell fermentation consists of higher batch cell density per batch. With more cells comes higher protein and increased product yield. The caveat with having a lot of cells is the process to remove it. The traditional method of cell removal proves to be inefficient.

Part of Anna Senczuk’s study was to determine how the flocculation method can be applied to remove solids from cell cultures. Flocculation is a technique that has been used for awhile in various industries, including waste water cleanup and pulp and paper.  As part of the cell removal project, Anna has been researching and developing a new and improved process using flocculation and tradition cell removal techniques.

In this project, Anna’s investigative goals included:

  • Understand how flocculation works in our processes
  • Could particle distribution analysis help optimize flocculation?
  • Is there a direct correlation between particle distribution and filterability?

Methods that Anna used in her investigation included FBRM (Focused Beam Reflectance Measurement), SHC filtration as an analytical method, and lipid assays (sieving and absorptive properties of filters).  FBRM is an in situ­ particle characterization tool that measures the cell flocs/debris as it naturally exists in process.  Real time measurements were then correlated to other techniques – such as filtration rate – to gain process understanding and allow for process optimization.

(I also discussed flocculation last week in my post: Why Is Canada Reducing Oil Sand Tailing Ponds?)