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Digital design and optimization of an integrated reaction-extraction-crystallization-filtration continuous pharmaceutical process

conference contribution
posted on 10.03.2022, 10:18 by Tim CampbellTim Campbell, Chris RiellyChris Rielly, Brahim BenyahiaBrahim Benyahia
This work investigates the digital design of a continuous pharmaceutical plant comprising a continuous three stage reaction, liquid-liquid extraction, multistage cooling and antisolvent crystallization, and wash-filtration. Firstly, the mathematical models were developed and validated in conjunction with the available experimental data obtained from the literature and research partners. The resulting digital twin was used for steady state optimization to deliver optimal options for plant design and operation, including process capacities and number of crystallization stages. After the identification of the optimal design and optimal steady state operation, the digital twin was used to perform uncertainty propagation and global sensitivity analysis to identify the Critical Process Parameters (CPP) and Critical Material Attributes (CMA) and deliver robust and cost-effective methods for a systematic implementation of Quality-by-Design (QbD). This approach is aimed at demonstrating that the plant can be operated within the robust quality bounds which provide a built-in quality assurance for the final product. Several Critical Quality Attributes (CQA) which impact drug safety and efficacy were considered which includes the average crystal size, crystal size distribution, coefficient of variation and product purity were considered as the CQA.



  • Aeronautical, Automotive, Chemical and Materials Engineering


  • Chemical Engineering

Published in

32nd European Symposium on Computer Aided Process Engineering: ESCAPE-32


32nd European Symposium on Computer Aided Process Engineering (ESCAPE32)




AM (Accepted Manuscript)

Rights holder

© Elsevier

Publisher statement

This paper was accepted for publication in the 32nd European Symposium on Computer Aided Process Engineering: ESCAPE-32 and the definitive published version is available at [insert DOI link].

Acceptance date


Book series

Computer Aided Chemical Engineering




Ludovic Montastruc, Stéphane Negny


Toulouse, France

Event dates

12th June 2022 - 15th June 2022


Dr Brahim Benyahia. Deposit date: 9 March 2022