Failure Mode Analysis of Continuous Process with Process Models

Failure Mode Analysis of Continuous Process with Process Models

 

Sze-Wing Wong[1], Prashant Kokitkar,  K. Derek Berglund, Martin D Johnson, and Shekhar K. Viswanath

Chemical Product R&D, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285

 

Abstract:  This presentation described the use of process models to drive process development of a continuous process at Eli Lilly and Company.  In this case study, the continuous process is represented with two separate models: a reaction kinetics model and a counter-current extraction model.  The reaction kinetics parameters were put into a three-in-series CSTR (Continuous Stirred Tank Reactor) model in which it can simulate different failure modes such as pump flow rate off-set or total pump failure.  The resulting impurity profile of the reaction mixture becomes the input to the counter-current extraction model where the equilibrium data of all the components at each stages is known.  With the combination of both process models, one can estimate how much process disturbances the system can handle.  The simulation results could then be used to identify potential critical process parameters and also be used to set the process control strategy.   This case study shows that the models can positively impact development of a continuous process even at early development phase, which is consistent with the quality by design principles.

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[1] Corresponding author

E-mail address: wongsz@lilly.com

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See more of this Session: Applications of Continuous Processing In Manufacture of Drug Substance
See more of this Group/Topical: Food, Pharmaceutical & Bioengineering Division