Knowledge Management and Process Monitoring of Pharmaceutical Processes in the Quality by Design Paradigm - Measurement, Monitoring, Modelling, and Control of Bioprocesses - page 246

4.3 Case Study 3: Real-Time Process Monitoring
As an example of real-time multivariate statistical process monitoring (RT-MSPM),
we present a case study involving development of a PCA-based model for monitoring
of a mammalian cell culture bioreactor at commercial scale [ 11 ]. Data were collected
during operation of a seed bioreactor train in a manufacturing plant. The dataset
consisted of 11 process variables that were measured online for 30 batches. The
resulting model was able to explain overall process variability with three principal
components. New production batches were then monitored against this model in real
time. The outcome of the analysis is illustrated in Fig. 25 . In step 1, a T 2 chart was
used to detect a deviation. Step 2 involved diagnosis at the variable level, which
indicated that the pH probe is reading less than historical averages, i.e. outside of ±3
SDs. Finally, in step 3, inspection of the pH trace was performed. This allowed
scientists and engineers to start troubleshooting the probe and other operational
factors to better understand and monitor the process via this simple three-step
process.
5 Conclusion
As the pharmaceutical industry implements QbD principles towards process and
product development and commercialization, it is critical that pharmaceutical
companies have an efficient and effective approach towards knowledge manage-
ment and process monitoring. The combination of data visualization and sophis-
ticated statistical techniques, such as those discussed in this chapter, and advanced
analytical tools will facilitate efficient process monitoring. This in turn will result
in increased consistency of product quality as well as efficiency in manufacturing
of pharmaceutical products and bring us closer to full implementation of QbD and
realizing its benefits.
References
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