Scale-Up of a Fed-Batch Bioreactor Process

Rapid 200 Fold Scale-Up of a Fed-Batch Bioreactor Process for a CHO Cell Line expressing a Mab

Benefits of Case:

  • A fed-batch bioreactor process of a CHO cell line was transferred from a client and scaled 200 fold with minimal process development evaluation and testing
  • Equivalent productivity profiles were obtained at 0.5, 3, and 100L bioreactor scale
  • A commercially available off the shelf chemically defined media and feed solution were utilized
  • Process Development costs and time were minimized

Background and Challenge:

  • The client had performed preliminary bioreactor runs at the 0.5 scale with the CHO cell line
  • The client required a rapid 200 fold scale-up to the 100L bioreactor level with minimal process development
  • Time constraints dictated that only two-3L bioreactor evaluations could be performed prior to scale-up to the 100L bioreactor
  • The clients’ 0.5L bioreactor system differed in design from the 3 and 100L bioreactor utilized for process development and scale-up

Strategy:

  • Utilize a commercially available off the shelf chemically defined media and feed solution used by the client at the 0.5L scale
  • Utilize process data from the 0.5L sale to design operating parameters for the 3L scale bioreactor although the 0.5 and 3L bioreactors differed in design
  • 3L process development and 100L scale bioreactor are of similar design and use the same control software

Development Data:

  • The most favorable integrated viable cell density was obtained with the 0.5L bioreactor most likely due to oxygen delivery rates
  • A productivity of 900mg of IgG/L at the 0.5 scale transferred to the 3 and 100L bioreactor scale was achieved
  • The feed schedule data from the 0.5L scale transferred to the 3 and 100L scale with only minor adjustments
  • Metabolic profiles were similar at all three bioreactor scales
  • Only two process development 3L bioreactor runs were required prior to scale-up of the process of the 100L bioreactor

Value for the Client:

  • A rapid 200 fold bioreactor scale-up was achieved with minimal process development
  • Use of a commercially available off the shelf chemically defined media and feed solution facilitated technology transfer and scale-up
  • Process development costs were minimalized and product launch accelerated