SUMMARY
An approach combining process and equipment characterization was used to transfer a high titer, fed-batch E. coli fermentation process for the production of Q-beta VLP rapidly and successfully from a collaborator to Pfizer's cGMP pilot
plant. The early assembly of an appropriately staffed and sized technology transfer team that enabled efficient communication
with the collaborator was key to the success of this endeavor. Based on a review of the fermentation process, high oxygen
demand during the fed-batch phase was identified as an important issue, especially if the fermentation was to be reproduced
without oxygen supplementation. The original fermentation process was rapidly transferred to a 15-L laboratory-scale fermentation
system, while simultaneously collecting process characterization data. Subsequently, equipment characterization of the cGMP
pilot plant and laboratory fermentation systems was undertaken. Based on these results, the original fermentation feeding
strategy was modified to decrease the duration of the pre-induction feed phase and lower peak oxygen demand. The resulting
fermentation process took advantage of the maximum oxygen transfer rate achievable in the pilot-scale fermenter, and successfully
produced Q-beta VLP at a sufficiently high titer without the need for oxygen enrichment of the process air stream.
ACKNOWLEDGMENTS
We would like to thank Cytos Biotechnology, Pfizer Vaccines Research Unit, Pfizer Bioprocess R&D Manufacturing and Analytical
R&D Group, Michael Dupuis, Aparna Deora, John Amery, David Steinmeyer and Tom Warren.
Shamik Sharma* is a principal scientist, Allison Whalley is a scientist, Joseph McLaughlin is an associate research fellow, Frank Brello is a senior scientist, Bruce Bishop is a an associate research fellow, and Amit Banerjee is a research fellow, all in the department of Biotherapeutics Pharmaceutical Sciences, Worldwide R&D at Pfizer Inc, Chesterfield
MO and Andover MA. *To whom corresepondance should be addressed: Shamik.Sharma@pfizer.com
.
PEER REVIEWED
Article submitted: Nov. 18, 2010.
Article accepted: Apr. 22, 2011.
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