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Fed‐batch bioreactor process scale‐up from 3‐L to 2,500‐L scale for monoclonal antibody production from cell culture
Author(s) -
Yang JengDar,
Lu Canghai,
Stasny Brad,
Henley Joseph,
Guinto Woodrow,
Gonzalez Carlos,
Gleason Joseph,
Fung Monica,
Collopy Brett,
Benjamino Michael,
Gangi Jennifer,
Hanson Melissa,
Ille Elisabeth
Publication year - 2007
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.21413
Subject(s) - bioreactor , scale up , aeration , process engineering , scale (ratio) , environmental science , process development , process (computing) , biochemical engineering , pulp and paper industry , computer science , chemistry , biology , engineering , ecology , physics , organic chemistry , classical mechanics , quantum mechanics , operating system
This case study focuses on the scale‐up of a Sp2/0 mouse myeloma cell line based fed‐batch bioreactor process, from the initial 3‐L bench scale to the 2,500‐L scale. A stepwise scale‐up strategy that involved several intermediate steps in increasing the bioreactor volume was adopted to minimize the risks associated with scale‐up processes. Careful selection of several available mixing models from literature, and appropriately applying the calculated results to our settings, resulted in successful scale‐up of agitation speed for the large bioreactors. Consideration was also given to scale‐up of the nutrient feeding, inoculation, and the set‐points of operational parameters such as temperature, pH, dissolved oxygen, dissolved carbon dioxide, and aeration in an integrated manner. It has been demonstrated through the qualitative and the quantitative side‐by‐side comparison of bioreactor performance as well as through a panel of biochemical characterization tests that the comparability of the process and the product was well controlled and maintained during the process scale‐up. The 2,500‐L process is currently in use for the routine clinical production of Epratuzumab in support of two global Phase III clinical trials in patients with lupus. Today, the 2,500 L, fed‐batch production process for Epratuzumab has met all scheduled batch releases, and the quality of the antibody is consistent and reproducible, meeting all specifications, thus confirming the robustness of the process. Biotechnol. Bioeng. 2007; 98: 141–154. © 2007 Wiley Periodicals, Inc.