Method for control, monitoring and/or optimization of a chromatographic process

A method for control and/or monitoring and/or optimization of a chromatographic process, in which the chromatographic process uses only two columns, consisting of a first column and a second column, the first column having a first column inlet and a first column outlet, the second column having a second column inlet and a second column outlet,

• the two columns being operated in said chromatographic process for an isolation of target molecules from a feed consisting of the target molecules and impurities to be separated from the target molecules using the following steps in order:
• a first batch step, performed during a batch timespan, wherein
• the two columns are disconnected,
• the first column is loaded with the feed via the first column inlet at a first flow rate and the first column outlet is directed to a waste, and
• from the second column, the target molecules are recovered via the second column outlet based on the second column being subjected to a regeneration process;
• a first interconnected step, performed during an interconnected timespan, wherein
• the first column outlet is connected to the second column inlet, the first column thus being a first upstream column and the second column thus being a first downstream column,
• the first column has a dynamic breakthrough capacity of the target molecules beyond which the target molecules exit the first column via the first column outlet,
• the first column is loaded beyond the dynamic breakthrough capacity with the feed via the first column inlet,
• the second column outlet is directed to the waste, and
• wherein during a subsequent washing timespan,
• the first column outlet remains connected to the second column inlet,
• the first column and the second column are subjected to a subsequent washing process by washing with a subsequent-washing-solvent, and/or a subsequent-washing-buffer, and
• an eluate exiting the second column outlet is directed to the waste;
• said first batch step and first interconnected step forming a first cycle,
• a second batch step, during which the two columns are disconnected and wherein the first column performs all tasks of the second column in the first batch step, and the second column performs all tasks of the first column in the first batch step;
• and
• a second interconnected step, wherein the second column outlet is connected to the first column inlet, the first column performs all tasks of the second column in the first interconnected step and the second column performs all tasks of the first column in the first interconnected step,
• said second batch step and second interconnected step forming a subsequent cycle,
• wherein downstream of each column, a detector is located at said first and second column outlets capable of detecting said target molecules and/or said impurities,
• wherein the method comprises the following steps:
• (a) measuring disconnected areas (Apeaki) corresponding to effluents of one or of two columns in a product elution position in a disconnected state in at least one cycle or parts of one cycle using the detectors at the column outlets, followed by at least the following step,
• (b) using the measured values of the disconnected areas (Apeaki) in said step (a) of the two detectors for control and/or monitoring and/or optimization of at least one process parameter,
• wherein the columns are loaded such that the initially determined disconnected area (Apeaki) is smaller than 80% of a maximum disconnected area (Apeaki,max) that is expected or known from previous chromatographic runs or cycles or parts thereof of the same chromatographic run, and
• wherein operating parameters are changed from cycle to cycle or multiples or parts thereof, such that a column load (L) is maximized while a ratio of the corresponding disconnected area (Apeaki,n) and the column load remains constant at a level defined by the column load and the disconnected area (Apeaki) in said step (a).

A method for control and/or monitoring and/or optimization of a chromatographic process, in which the chromatographic process uses only two columns, consisting of a first column and a second column, the first column having a first column inlet and a first column outlet, the second column having a second column inlet and a second column outlet,

• the two columns being operated in said chromatographic process for an isolation of target molecules from a feed consisting of the target molecules and impurities to be separated from the target molecules using the following steps in order:
• a first batch step, performed during a batch timespan, wherein
• the two columns are disconnected,
• the first column is loaded with the feed via the first column inlet at a first flow rate and the first column outlet is directed to a waste, and
• from the second column, the target molecules are recovered via the second column outlet based on the second column being subjected to a regeneration process;
• a first interconnected step, performed during an interconnected timespan, wherein
• the first column outlet is connected to the second column inlet, the first column thus being a first upstream column and the second column thus being a first downstream column,
• the first column has a dynamic breakthrough capacity of the target molecules beyond which the target molecules exit the first column via the first column outlet,
• the first column is loaded beyond the dynamic breakthrough capacity with the feed via the first column inlet,
• the second column outlet is directed to the waste, and
• wherein during a subsequent washing timespan,
• the first column outlet remains connected to the second column inlet,
• the first column and the second column are subjected to a subsequent washing process by washing with a subsequent-washing-solvent, and/or a subsequent-washing-buffer, and
• an eluate exiting the second column outlet is directed to the waste;
• said first batch step and first interconnected step forming a first cycle,
• a second batch step, during which the two columns are disconnected and wherein the first column performs all tasks of the second column in the first batch step, and the second column performs all tasks of the first column in the first batch step;
• and
• a second interconnected step, wherein the second column outlet is connected to the first column inlet, the first column performs all tasks of the second column in the first interconnected step and the second column performs all tasks of the first column in the first interconnected step,
• said second batch step and second interconnected step forming a subsequent cycle,
• wherein downstream of each column at said first and second column outlets, a detector is located capable of detecting said target molecules and/or said impurities, wherein the method comprises the following steps:
• (1) measuring interconnected areas (AICiU) corresponding to effluents of one or of two columns in an interconnected state in at least one cycle or parts of one cycle using the detectors at the column outlets;
• and
• (2) using the measured values of the interconnected areas (AICiU) in said step (1) of one or both detectors for control and/or monitoring of at least one process parameter, based on the measured values of the interconnected areas (AICiU) reaching a specific target set point value,
• wherein the process parameter is related to at least one of timing, flow rates, load, yield, recovery, throughput, and buffer consumption of the process, and
• wherein, when the process parameter reaches a pre-defined or automatically calculated set point value based on the measured values of the interconnected areas (AICiU), an interconnected loading phase is stopped and an interconnected washing step or a subsequent loading step is initiated.