Methods and systems for determining multi-column chromatography process configuration

A system for determining an optimum multi-column chromatography (MCC) configuration of an MCC process, the system comprising:

• a memory storing instructions;
• one or more Input/Output (I/O) interfaces;
• and
• one or more hardware processors coupled to the memory via the one or more I/O interfaces, wherein the one or more hardware processors are configured by the instructions to:
• receive or more of:
• feed characteristics, targets for some of one or more key performance measures of the MCC process, one or more MCC configurations of the MCC process, one or more column characteristics of each column of one or more columns present in each MCC configuration, and media characteristics of one or more chromatography media for use in each column of one or more columns;
• select a chromatography column (CC) process model set from a plurality of CC process model sets, based on the media characteristics of the one or more chromatography media for use in each column of the one or more columns and one or more components present in the feed, wherein each CC process model set comprises (i) a mobile phase mass transfer model and associated mobile phase model parameter (ii) a stationary phase mass transfer model and associated stationary phase parameters, and (iii) an adsorption-desorption model and associated adsorption-desorption parameters;
• determine through an optimization technique, values of one or more decision variables that optimizes the one or more key performance measures of the MCC process, to obtain optimized values of the one or more key performance measures, for each MCC configuration of the one or more MCC configurations, using the selected CC process model set, by:
• (a) generating initial values of the one or more decision variables, using the optimization technique;
• (b) obtaining sequence of chromatographic operations and a duration of each sequence of chromatographic operations at each stage of the MCC process, if the initial values of the one or more decision variables satisfies a feasibility criteria, wherein the feasibility criteria is associated with completion of regeneration protocol during a column switch and completion of predefined number of wash volumes;
• (c) calculating the one or more key performance measures of the MCC process by simulating the MCC process using the selected CC model set for the obtained sequence of chromatographic operations and the duration of the sequence of chromatographic operations, at each stage, until a cyclic steady state (CSS) of the MCC configuration is achieved, wherein in simulating the MCC process, inlet boundary condition for each of the column of the associated MCC configuration takes into account, the change in the operating conditions associated with each chromatographic operation and interconnected nature of column operations,
• wherein while simulating a wash operation and an elute operation, an inlet concentration cin is set equal to zero since monoclonal antibodies mAb is absent in the incoming buffer stream;
• wherein the one or more decision variables are associated with operating conditions to be maintained at each chromatographic operation of a set of chromatographic operations to be performed at each stage, and the one or more column characteristics of each column of one or more columns present in the MCC configuration;
• and
• determine the optimum MCC configuration out of one or more MCC configurations, based on the associated optimized values of the one or more key performance measures of the MCC process, wherein the optimum MCC configuration is determined before a physical design of the MCC configuration significantly decreasing an amount of time, a material cost invested for designing the optimum MCC configuration,
• wherein the design of the MCC configuration meets purification targets and optimizing the one or more key performance measures.

A computer program product comprising a non-transitory computer readable medium having a computer readable program embodied therein, wherein the computer readable program, when executed on a computing device, causes the computing device to:

• receive or more of:
• feed characteristics, targets for some of one or more key performance measures of the MCC process, one or more MCC configurations of the MCC process, one or more column characteristics of each column of one or more columns present in each MCC configuration, and media characteristics of one or more chromatography media for use in each column of one or more columns;
• select a chromatography column (CC) process model set from a plurality of CC process model sets, based on the media characteristics of the one or more chromatography media for use in each column of the one or more columns and one or more components present in the feed, wherein each CC process model set comprises (i) a mobile phase mass transfer model and associated mobile phase model parameter (ii) a stationary phase mass transfer model and associated stationary phase parameters, and (iii) an adsorption-desorption model and associated adsorption-desorption parameters;
• determine through an optimization technique, values of one or more decision variables that optimizes the one or more key performance measures of the MCC process, to obtain optimized values of the one or more key performance measures, for each MCC configuration of the one or more MCC configurations, using the selected CC process model set, comprises:
• (a) generating initial values of the one or more decision variables, using the optimization technique;
• (b) obtaining sequence of chromatographic operations and a duration of each sequence of chromatographic operations at each stage of the MCC process, if the initial values of the one or more decision variables satisfies a feasibility criteria, wherein the feasibility criteria is associated with completion of regeneration protocol during a column switch and completion of predefined number of wash volumes;
• (c) calculating the one or more key performance measures of the MCC process by simulating the MCC process using the selected CC model set for the obtained sequence of chromatographic operations and the duration of the sequence of chromatographic operations, at each stage, until a cyclic steady state (CSS) of the MCC configuration is achieved, wherein in simulating the MCC process, inlet boundary condition for each of the column of the associated MCC configuration takes into account, the change in the operating conditions associated with each chromatographic operation and interconnected nature of column operations,
• wherein while simulating a wash operation and an elute operation, an inlet concentration cin is set equal to zero since monoclonal antibodies mAb is absent in the incoming buffer stream;
• wherein the one or more decision variables are associated with operating conditions to be maintained at each chromatographic operation of a set of chromatographic operations to be performed at each stage, and the one or more column characteristics of each column of one or more columns present in the MCC configuration;
• determine the optimum MCC configuration out of one or more MCC configurations, based on the associated optimized values of the one or more key performance measures of the MCC process, wherein the optimum MCC configuration is determined before a physical design of the MCC configuration significantly decreasing an amount of time, a material cost invested for designing the optimum MCC configuration,
• wherein the design of the MCC configuration meets purification targets and optimizing the one or more key performance measures;
• and
• display the optimal MCC configuration and along with the values of one or more decision variables associated with the optimized values of the one or more key performance measures through a display unit.