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Conversion of a CHO cell culture process from perfusion to fed-batch technology without altering product quality

Paper ID Volume ID Publish Year Pages File Format Full-Text
25784 43599 2006 11 PDF Available
Title
Conversion of a CHO cell culture process from perfusion to fed-batch technology without altering product quality
Abstract

During the development of a new drug product, it is a common strategy to develop a first-generation process with the aim to rapidly produce material for pre-clinical and early stage clinical trials. At a later stage of the development, a second-generation process is then introduced with the aim to supply late-stage clinical trials as well as market needs.This work was aimed at comparing the performance of two different CHO cell culture processes (perfusion and fed-batch) used for the production of a therapeutically active recombinant glycoprotein at industrial pilot-scale. The first-generation process was based on the Fibra-Cel® packed-bed perfusion technology. It appeared during the development of the candidate drug that high therapeutic doses were required (>100 mg per dose), and that future market demand would exceed 100 kg per year. This exceeded by far the production capacity of the first-generation process, and triggered a change of technology from a packed-bed perfusion process with limited scale-up capabilities to a fed-batch process with scale-up potential to typical bioreactor sizes of 15 m3 or more.The productivity per bioreactor unit volume (in product m−3 year−1) of the fed-batch process was about 70% of the level reached with the first-generation perfusion process. However, since the packed-bed perfusion system was limited in scale (0.6 m3 maximum) compared to the volumes reached in suspension cultures (15 m3), the fed-batch was selected as second-generation process. In fact, the overall process performance (in product year−1) was about 18-fold higher for the fed-batch compared to the perfusion mode.Data from perfusion and fed-batch harvests samples indicated that comparable product quality (relative abundance of monomers dimers and aggregates; N-glycan sialylation level; isoforms distribution) was obtained in both processes. To further confirm this observation, purification to homogeneity of the harvest material from both processes, followed by a complementary set of studies (e.g. full physico-chemical characterization, assessment of in vitro and in vivo bioactivity, comparative pharmacokinetics and pharmacodynamics studies in relevant species, etc.) would be required.Finally, this illustrates the need to fix the production process early during the development of a new drug product in order to minimize process conversion efforts and to shorten product development timelines.

Keywords
Perfusion; Fed-batch; CHO; Productivity; Quality
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Conversion of a CHO cell culture process from perfusion to fed-batch technology without altering product quality
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 123, Issue 1, 3 May 2006, Pages 106–116
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us