An Advanced Monitoring Platform for Rational Design of Recombinant Processes - Measurement, Monitoring, Modelling, and Control of Bioprocesses - page 81

permits improved process stability and increases the host cell's capacity for
recombinant gene expression, resulting in higher product yields [ 66 ].

6 Conclusions

The established integrated approach for process and systems optimization is
mainly based on a process monitoring platform. This platform significantly con-
tributes to improve process understanding and to implement PAT and QbD con-
cepts in bioprocessing. Moreover, the platform approach complies with
pharmaceutical quality guidelines, in particular with ICH Q8, aiming at increasing
product and manufacturing knowledge, which in turn will decrease the time
required for marketing authorization.
Using the platform in combination with modeling techniques and predictive
soft sensors, new and better process control strategies and improved process
performance can be accomplished. Variables otherwise only available offline can
be acquired in real time, enabling novel control regimes; For instance, real-time
access to CDM could allow implementation of a model-based inducer feeding
regime, and thereby the unwanted effects of increasing inducer/CDM ratios can be
eliminated by using the established transcription tuning concept. This strategy
could also allow growth of cells under conditions that have not been practically
possible to date, where detailed analysis of such cells could deliver new insights
into their metabolism.
Iterative process and systems optimization generates knowledge on the process
and the cellular system. Based on the improved understanding of the cellular
response to recombinant gene expression, such as metabolic bottlenecks, imbal-
ances in the supply of building blocks, and interaction of the recombinant protein
with the host metabolism, rational design of the host cell and process operation is
possible.

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