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Open-loop control of the biomass concentration within the growth phase of recombinant protein production processes

Paper ID Volume ID Publish Year Pages File Format Full-Text
25562 43581 2006 11 PDF Available
Title
Open-loop control of the biomass concentration within the growth phase of recombinant protein production processes
Abstract

Recombinant protein production processes are typically divided into two phases. In the first one, pure cell propagation takes place, while in the second one product formation is switched on within the cells by adding an inducer. In the initial biomass formation phase, the cell density is rather low and, hence, the measurement quantities that could be used to determine the process’ state depict small values and are rather severely distorted by measurement noise. Because of these measurement problems, the fermentation cannot be reliably controlled by feedback control during this first production phase; instead, the process must be controlled in an open-loop fashion. The consequence, worked out in this paper, is to design substrate feed rate profiles for the growth phase in such a way that they are robust with respect to the main disturbances observed in practice. The robustness of the biomass formation is shown to be primarily dependent on the specific growth rate adjusted in the first hours. High batch-to-batch reproducibility can be obtained with exponential feeding profiles F(t) corresponding to specific growth rates μset well below the maximal specific growth rate μmax of the organism. The reduction in the growth rate needed to obtain a robust process behavior depends on the inaccuracies in the initial biomass concentrations. Quantitative feed rate profiles were obtained by numerical simulation and these results were validated experimentally by means of a series of cultivation runs, where a recombinant pharmaceutical protein was produced. All experimental data confirmed the assumptions made in the robust process design study.

Keywords
Open-loop control; PAT; Reproducible recombinant protein production; Statistical process analysis
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Open-loop control of the biomass concentration within the growth phase of recombinant protein production processes
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 127, Issue 1, 15 December 2006, Pages 84–94
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