Quality risk management for pharmaceutical manufacturing: The role of process modeling and simulations

This chapter discusses the use of process models to support quality risk management in pharmaceutical manufacturing. It starts with describing the elements of quality risk management, and then outlines how process models can aid the risk assessment process through sensitivity analysis and the evaluation of risk mitigation strategies through feasibility analysis. It then discusses different categories of process models based on their impact on product quality assurance, and the scientific considerations that may need to be taken into account to incorporate these process models into the quality risk management system. Finally, several case studies of continuous manufacturing are presented, illustrating the potential role of process models in the implementation of emerging manufacturing technologies.

[1]  Marianthi G. Ierapetritou,et al.  An integrated approach for dynamic flowsheet modeling and sensitivity analysis of a continuous tablet manufacturing process , 2012, Comput. Chem. Eng..

[2]  John F. MacGregor,et al.  Modeling and Optimization of a Tablet Manufacturing Line , 2011, Journal of Pharmaceutical Innovation.

[3]  Lawrence X. Yu,et al.  Modernizing Pharmaceutical Manufacturing: from Batch to Continuous Production , 2015, Journal of Pharmaceutical Innovation.

[4]  Jack P. C. Kleijnen,et al.  Kriging Metamodeling in Simulation: A Review , 2007, Eur. J. Oper. Res..

[5]  Marianthi G. Ierapetritou,et al.  Modeling of Particulate Processes for the Continuous Manufacture of Solid-Based Pharmaceutical Dosage Forms , 2013 .

[6]  Antonello Barresi,et al.  Development of simplified models for the freeze-drying process and investigation of the optimal operating conditions , 2008 .

[7]  Davide Fissore,et al.  On the use of mathematical models to build the design space for the primary drying phase of a pharmaceutical lyophilization process. , 2011, Journal of pharmaceutical sciences.

[8]  Lilli Møller Andersen,et al.  Quality Risk Management , 2021, Handbook of Pharmaceutical Manufacturing Formulations, Second Edition.

[9]  Christodoulos A. Floudas,et al.  Global Optimization in Design under Uncertainty: Feasibility Test and Flexibility Index Problems , 2001 .

[10]  Marianthi G. Ierapetritou,et al.  An Integrated Approach to Simulation of Pharmaceutical Processes for Solid Drug Manufacture , 2014 .

[11]  Marianthi Ierapetritou,et al.  System-wide hybrid MPC-PID control of a continuous pharmaceutical tablet manufacturing process via direct compaction. , 2013, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[12]  H Leuenberger,et al.  New trends in the production of pharmaceutical granules: batch versus continuous processing. , 2001, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[13]  Richard D. Braatz,et al.  Model‐based design of a plant‐wide control strategy for a continuous pharmaceutical plant , 2013 .

[14]  I. Sobola,et al.  Global sensitivity indices for nonlinear mathematical models and their Monte Carlo estimates , 2001 .

[15]  Ignacio E. Grossmann,et al.  Design optimization of stochastic flexibility , 1993 .

[16]  K. Plumb,et al.  Continuous Processing in the Pharmaceutical Industry: Changing the Mind Set , 2005 .

[17]  Marianthi G. Ierapetritou,et al.  Feasibility analysis of black-box processes using an adaptive sampling Kriging-based method , 2012, Comput. Chem. Eng..

[18]  Marianthi Ierapetritou,et al.  Implementation of an advanced hybrid MPC-PID control system using PAT tools into a direct compaction continuous pharmaceutical tablet manufacturing pilot plant. , 2014, International journal of pharmaceutics.

[19]  Marianthi G. Ierapetritou,et al.  Feasibility Evaluation of Nonconvex Systems Using Shape Reconstruction Techniques , 2005 .

[20]  G. K. Raju,et al.  Understanding Pharmaceutical Quality by Design , 2014, The AAPS Journal.

[21]  Marianthi G. Ierapetritou,et al.  A systematic framework for onsite design and implementation of a control system in a continuous tablet manufacturing process , 2014, Comput. Chem. Eng..

[22]  Fani Boukouvala,et al.  Computer-Aided Flowsheet Simulation of a Pharmaceutical Tablet Manufacturing Process Incorporating Wet Granulation , 2013, Journal of Pharmaceutical Innovation.

[23]  Marianthi G. Ierapetritou,et al.  Determination of operability limits using simplicial approximation , 2002 .

[24]  Anwesha Chaudhury,et al.  Flowsheet optimization of an integrated continuous purification-processing pharmaceutical manufacturing operation , 2013 .

[25]  Fernando J. Muzzio,et al.  Flowsheet models modernize pharmaceutical manufacturing design and risk assessment , 2015 .

[26]  D. T. Witte,et al.  Examples of NIR based real time release in tablet manufacturing. , 2007, Journal of pharmaceutical and biomedical analysis.

[27]  J. Macgregor,et al.  Scale-up of a Pharmaceutical Roller Compaction Process Using a Joint-Y Partial Least Squares Model , 2011 .

[28]  Tomas Skoglund,et al.  Fuzzy traceability: A process simulation derived extension of the traceability concept in continuous food processing , 2007 .

[29]  Günter Wozny,et al.  A Modular Approach to Sustainability Assessment and Decision Support in Chemical Process Design , 2010 .

[30]  Gintaras V. Reklaitis,et al.  Intelligent Process Management for Continuous Operations in Pharmaceutical Manufacturing , 2014 .