Structured Modelling of Chemical Processes : An Object-Oriented Approach

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Optimization study on periodic counter-current chromatography (PCC) integrated in a mAb downstream process

In the biopharmaceutical market, there is an increasing pressure to reduce prices. Nowadays, a big part of the manufacturing cost is due to the product purification. A big effort has been made in this matter to reduce costs, and continuous downstream processes like periodic counter-current chromatography (PCC) have gained interest in the last years due to a higher productivity and resin utilization compared to a batch process. Herein, a PCC process is integrated with a virus inactivation and two ion-exchange chromatography steps (polishing steps) for the purification of mAb at lab scale, and multi-objective optimization is used to compare several process configurations using two resins with different particle sizes. Please click Additional Files below to see the full abstract

Method development in inverse modeling applied to supercritical fluid extraction of lipids

Modeling of the supercritical fluid extraction of solid materials is an important aspect in order to understand and predict the process. A comparison of two empirical models, two semi-empirical models and two mechanistic models is performed using calibration of single experiments. It is concluded that the best fit is obtained using a simple empirical expression. Furthermore, single calibrations did not generate reliable parameters with physical meaning and a methodology is proposed for inverse modeling with complete calibration using several experiments. The experimental dataset contained 29 extractions of lipids from crushed linseeds with varying temperatures, pressures and flow rates. A general rate model and a proposed extension of the hot ball model were evaluated for this purpose. The methodology includes data acquisition, model structure estimation, model calibration and a cross-validation. In general, it was found that the solubility model of Sovová outperformed the other evaluated correlations, and for the general rate model the Toth partition isotherm was also found in the top model structures. However, no generalization could be made regarding the correlations describing the Nernst diffusion layer and diffusivity

Supervisory control of integrated continuous downstream processes

Smart downstream processing can be performed with a sequence of integrated purification steps, which minimize the number of storage tanks and reduce hold-up time. The result is an integrated unit operation sequence that performs straight through processing of the target protein, with minimal time from expression to formulation. This downstream processing technique is well suited to be connected to a continuous upstream process based on perfusion. To develop these kinds of processes it is important to do studies in small-scale in a convenient way. This paper presents a methodology for supervisory control of integrated continuous downstream processes in lab-scale. A general platform in lab-scale for sequential processing of integrated downstream processes is developed using ÄKTA/UNICORN-systems. The modification of the physical setup to handle multiple processing steps in sequence on one single machine makes it possible to study advanced and complex process configurations without a lot of resources. To make it easy to program and run the complicated setup a new supervisory controller is developed on top of UNICORN. The new controller, called orbit, is extendable and flexible to handle very different configurations and processes. To facilitate the usage even further the actual controller code is automatically generated from a high level presentation of the separation problem. Tools for design, control and verification makes it possible to virtual test the concept before making the actual experiment. The power of this concept is illustrated by some case studies. Please click Additional Files below to see the full abstract

Conversion of an industrial batch separation process to an autonomous integrated downstream process – A case study

In this contribution an industrial case study, consisting of several unit operations operated in batch mode, was converted to an integrated separation process. The complete downstream process consisted of an anion exchange step, followed by virus inactivation and finally a hydrophobic interaction step. Moving from batch to integrated separation minimizes hold-up times, storage tanks and required equipment. The conversion from batch to integrated mode was achieved by extracting operating points and separation data from batch chromatograms. The integrated separation process was realized on an ÄKTA Pure controlled by a newly developed software called Orbit. The setup consisted of two column valves which were used alternatively. In order to send the sample or the buffers from one column to another, two versatile valves were used before and after the column valves. In addition, an outlet valve after the second versatile valve sent the pool back to the first versatile valve to begin a new phase. Orbit works on top of UNICORN through an OPC interface. The new controller is very flexible and can handle different column configurations. There is great power in being able to control every valve and pump. This is exploited by Orbit which allows both high and low level inputs. High level inputs are operating conditions (i.e flow rate and flow path). The high level inputs are automatically transformed into low level inputs (i.e. valve positions) that the OPC server can read. The processes that can be controlled are among others end-to-end downstream processes as well as integrated filtration systems such as UF/D

Conversion of an industrial batch separation process to an autonomous integrated downstream process – A case study Anton Lofgren, Lund University, Sweden

In this contribution an industrial case study, consisting of several unit operations operated in batch mode, was converted to an integrated separation process. The complete downstream process consisted of an anion exchange step, followed by virus inactivation and finally a hydrophobic interaction step. Moving from batch to integrated separation minimizes hold-up times, storage tanks and required equipment. The conversion from batch to integrated mode was achieved by extracting operating points and separation data from batch chromatograms. The integrated separation process was realized on an ÄKTA Pure controlled by a newly developed software called Orbit. The setup consisted of two column valves which were used alternatively. In order to send the sample or the buffers from one column to another, two versatile valves were used before and after the column valves. In addition, an outlet valve after the second versatile valve sent the pool back to the first versatile valve to begin a new phase. Orbit works on top of UNICORN through an OPC interface. The new controller is very flexible and can handle different column configurations. There is great power in being able to control every valve and pump. This is exploited by Orbit which allows both high and low level inputs. High level inputs are operating conditions (i.e flow rate and flow path). The high level inputs are automatically transformed into low level inputs (i.e. valve positions) that the OPC server can read. The processes that can be controlled are among others end-to-end downstream processes as well as integrated filtration systems such as UF/DF