A robust cell culture production process should demonstrate consistency not only in product quality but also in production yields. Potential sources of variability in cell specific productivity upon thaw of frozen cell stock were investigated by reviewing, prioritizing and performing statistical analyses on inputs to cell expansion campaigns used to generate the frozen cell stock. These included, raw materials (biological, chemical and consumables), operations (equipment, personnel and procedures – including sampling and testing) and the environmental conditions at the facility. Inputs affecting the state of the cells at early steps of the cell expansion process (from vial thaw, through T-flasks and roller bottles) including the master cell source itself were ruled out. This led us to focus on operating parameters serving as inputs during perfusion bioreactor unit operation – the last phase of the cell expansion process prior to generation of the frozen cell stock. Multivariate analysis (MVA) suggested that an operational parameter of the cell retention device is the primary process-input affecting variability in cell specific productivity during steady state perfusion culture. This finding was consolidated with scientific rationale into a testable hypothesis. Changes to the set point of the cell retention device parameter were tested and confirmed a higher and less variable specific productivity while meeting process and product quality requirements.

Reducing variability in cell specific productivity in perfusion culture

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.