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In this paper, we describe POP, a MATLAB toolbox for parametric optimization. It features (a) efficient implementations of multiparametric programming problem solvers for multiparametric linear and quadratic programming problems and their mixed-integer counter-parts, (b) a versatile problem generator capable of creating random multiparametric programming problems of arbitrary size, and (c) a comprehensive library of multiparametric programming test problems featuring benchmark test sets for multiparametric linear, quadratic, mixed-integer linear, and mixedinteger quadratic programming problems. In addition, POP is equipped with a graphical user interface which enables the userfriendly use of all functionalities of POP and a link to the solvers of the Multi-Parametric Toolbox (MPT), as well as the ability to design explicit MPC problems. These features are demonstrated in detailed computational studies providing insights into the versatility and applicability of POP. Additionally, the example of a periodic chromatographic system is used to show the scalability of multiparametric programming in general and POP, in particular.Article pubs.acs.org/IECR

The multicolumn countercurrent solvent gradient purification process (MCSGP) is a semicontinuous, chromatographic separation process used in the production of monoclonal antibodies) . The process is characterized by high model complexity and periodicity that challenge the development of control strategies, necessary for feasible and efficient operation and essential toward continuous production. A novel approach for the development of control policies for the MCSGP process, which enables efficient continuous process control is presented. Based on a high fidelity model, the recently presented PAROC framework and software platform that allows seamless design and in-silico validation of advanced controllers for complex systems are followed. The controller presented in this work is successfully tested against disturbances and is shown to efficiently capture the process periodic nature. V C 2016 American Institute of Chemical Engineers AIChE J, 62: 2341AIChE J, 62: -2357AIChE J, 62: , 2016 Keywords: process control, continuous biomanufacturing, multiparametric control IntroductionMonoclonal antibodies (mAbs) play a vital role in the treatment of infectious diseases, cancer, and autoimmune diseases.1 They are characterized, however, by high prices (approximately $35000 p/a per patient for mAbs treating cancer conditions) 2 that arise from their high production costs. Although over the past few years their market has been rapidly increasing, 3 the emergence of biosimilars and the introduction of novel therapeutic agents drives their biomanufacturing toward alternative routes of lower operating costs. 4 MAb production consists of the upstream processing (USP), where the cells are cultured and the therapeutic agent is produced, and the downstream processing (DSP) that involves the isolation/ purification steps of the targeted product. Under high titers, however, DSP can become significantly expensive, mostly due to equipment and consumables costs. [5][6][7][8][9] This along with the increasing demand on product quality and higher titers 3,5 drive advances in mAb biomanufacturing toward continuous operation. 4 Here, we focus on the development of advanced control strategies for the multicolumn countercurrent solvent gradient purification process (MCSGP), 10 aiming to drive the system toward continuous operation. MCSGP is a semicontinuous, chromatographic separation process of biomolecules, based on ion-exchange firstly presented by . 11 The process is described by complex partial differential and algebraic equations (PDAEs), involving highly nonlinear terms and is governed by periodic operation profiles that render control studies difficult to perform. There have been several works that have studied the optimization and control of such systems. Degerman et al. (2006) 12 use a nonlinear performed optimization studies on a nonlinear chromatography model to define the optimal operation points that will meet the purity Corresponding concerning this article should be addressed to E. Pistikopoulos at stratos@tamu.edu. constrai...