AUTOMATED SIMULTANEOUS PROCESS CONTROL

Abstract

Described herein is a method and a system for automated simultaneous control of at least two process characteristics of a continuous production process with at least one fluid stream, at least two unit operations, at least one process control system and at least one conditioning volume.

Claims

1. A method for automated simultaneous control of at least two process characteristics of a continuous production process with at least one fluid stream, at least two unit operations, at least one process control system and at least one conditioning volume, comprising at least one of the following a) at least one subsystem for automatically controlling at least two actuators which influence the same conditioning volume and/or a) at least one subsystem for automatically influencing at least one actuator based on a combination of feed forward regulation and feedback control.

2. The method according to claim 1, wherein a) if the method comprises at least one subsystem for automatically controlling at least two actuators which influence the same conditioning volume the at least one subsystem for automatically controlling at least two actuators which influence the same conditioning volume controls the at least two process characteristics via detecting simultaneously at least two characteristics of the fluid stream via at least two independent sensors calculating at least two actuating values, one for each of the at least two measured characteristics, in the at least on process control system influencing via said at least two actuating values at least two actuators, and/or b) if the method comprises at least one subsystem for automatically influencing at least one actuator based on a combination of feed forward regulation and feedback control the at least one subsystem for automatically influencing at least one actuator based on a combination of feed forward regulation and feedback control influences the at least one process characteristics via detecting at least one feature of at least one conditioning volume upstream of one of the at least two unit operations with at least one sensor detecting at least one feature related to the loading of the said one of the at least two unit operations calculating at least one actuating value in the at least on process control system based on the detected at least one feature of at least one conditioning volume upstream of the said one of the at least two unit operations as well as the at least one feature related to the loading of the said one of the at least two unit operation influencing the at least one actuator via said at least one actuating value wherein said influencing of the actuator is thus based on a combination of feed forward regulation derived from the at least one detected feature related to the loading of the one said of the at least two unit operations and feedback control derived from the at least one detected feature of at least one conditioning volume.

3. The method according to claim 1 wherein said method comprises at least one subsystem for automatically controlling at least two actuators which influence the same conditioning volume the method a) further comprises transmitting said at least two characteristics of the fluid stream detected by the at least two independent sensors as signals to at least two converters which convert the signals to converted signals and transmitting the at least two converted signals to the at least one process control system.

4. The method according to claim 3 wherein the method a) comprising the at least one subsystem for automatically controlling at least two actuators which influence the same conditioning volume further comprises comparing in the at least one process control system said at least two converted signals, which correspond to at least two actual process characteristics, with at least two set values for the same process characteristics, calculating the at least two actuating values in the process control system based on said comparison as well as additional calculations.

5. The method according to claim 1 comprising at least two subsystems.

6. A system for automated control of at least two process characteristics of a fluid stream of a continuous production process with at least two unit operations, at least one process control system and at least one conditioning volume, comprising at least one of the following a) at least one subsystem for automatically controlling at least two actuators simultaneously which influence the same conditioning volume comprising at least two independent sensors detecting simultaneously at least two characteristics of the fluid stream and at least one process control system which based on said at least two characteristics of the fluid stream calculates at least two actuating values, one for each of the at least two measured characteristics, which influence at least two actuators, and/or b) at least one subsystem for automatically influencing at least one actuator based on a combination of feed forward regulation and feedback control comprising at least one conditioning volume upstream of the at least two unit operations with at least one sensor for a feature of the at least one conditioning volume as well as at least one sensor for loading of the said at least one unit operation and at least one actuator influencing the said at least one unit operation

7. The system according to claim 6, further comprising at least one a subsystem for matching of the flow rates of a slave unit to the flow rate of another slave unit or master units with the proviso that in the case of several master units an auxiliary stream is opened, and comprising at least one master unit and at least one slave unit wherein each slave unit influences at least one buffer volume wherein each buffer volume is provided in the form of a surge tank and/or expandable tubing, as well as at least one sensor for each buffer volume.

8. The system according to claim 6, wherein the at least one subsystem for automatically controlling at least two actuators simultaneously which influence the same conditioning volume further comprises at least two converters to which the at least two independent sensors transmit said at least two characteristics of the fluid stream in the form of at least two signals and which then convert the at least two signals and transmit the at least two converted signals to the at least one process control system.

9. The system according to claim 6, wherein the continuous production process is a continuous production process for biomolecules.

10. The system according to claim 6, wherein the fluid stream is a continuous fluid stream.

11. The system according to claim 6 wherein at least two characteristics of the fluid stream and at least one feature of at least one conditioning volume are automatically and simultaneously controlled.

12. The system according to claim 6, wherein one of the at least two unit operations is a chromatography and the process control system employs a softsensor.

Description

FIGURES

[0139] FIG.1 shows a schematic diagram of the at least one subsystem for automatically controlling at least two actuators which influence the same conditioning volume. Here two process characteristics and one feature of at least one conditioning volume are controlled simultaneously. In the example the intermediate input, i.e. the process stream coming from the first of the at least two unit operations has a volumetric flow of 100% and a pH of 3. This pH of 3 has to be in the range of 5 when the product stream leaves the conditioning volume (termed conditioning intermediate bag in FIG. 1). The pH sensor measures the pH in the circulated fluid flow and/or in the surge bag and the process control system (PCS) recognizes the deviation between pH 3 and pH 5 and thus sets the speed of the actuator—here the pump delivering the pH set agent—according to the calculated actuating value, to alter the actual process characteristic, i.e. the pH to a value of approximately 5. Simultaneously, the conductivity (CD) sensor is detecting the conductivity in the circulated fluid flow in the homogenization loop and/or in the surge bag. Thus, the CD sensor will detect the change in conductivity due to the addition of pH set up agent. Consequently, the process control system (PCS) recognizes the deviation between the set value for the conductivity and the actual detected process characteristic for conductivity and thus sets the speed of the pump delivering the conductivity set agent according to the calculated actuating value to a rate which allows to counteract the influence (disturbance) of the pH set agent on the conductivity. For example the pump delivering the conductivity set agent e.g. water is automatically set to 240% (2.4×) of the incoming volumetric flow. Overall, due to the addition of pH-set agent and conductivity set agent the intermediate output, i.e. the process stream leaving the conditioning volume has a volume of 350% of the volume of the intermediate input. To a skilled person it is thus clear that simultaneously in this respect refers to the fact that all three control circuits are active at the same time hence not only enabling a simultaneous but also a real time control.

[0140] FIG. 2 shows a schematic diagram of a part of the at least one subsystem for automatically controlling at least two actuators which influence the same conditioning volume. In this example the pH actuating value and the conductivity actuating value are calculated by the process control system via employing at least one cascade feedback controller in combination with at least one feed forward regulation.

[0141] Moreover, in a specific example of this embodiment the set pH value in the conditioning volume should be 5.5. Thus, the “setpoint real” is 5.5 and this setpoint value is specified by the process control system to controller 1. Controller 1 is a controller comprising P (proportional) and I (integral) elements i.e. a PI controller. The input of controller 1 in the process control system is based on a pH sensor reading in the conditioning volume. The output of controller 1 is used for additional calculations. The additional calculations also take a disturbance e.g. a speed of a feed pump—as a feed forward into account, which is added to the set point real and results in the corrected/artificial set point for the second controller. The system is “disturbed” by the feed pump whenever additional process stream with a different pH value arrives at the conditioning volume or if other components such as pH set agent or water that alter the conductivity are added. In order to compensate for this potential disturbance, additional calculations are carried out i.e. in this case the speed of the feed pump conveying process stream into the conditioning volume is used as correction factor (also termed corrected/artificial setpoint) and is multiplied with the output of controller 1. Both values together act as input to controller 2. Hence, in case the feed pump has a speed of 2 and the output of controller 1 is 0.1 a value of 0.2 is added to the pH set point real and controller 2 bases its calculation of the actuating value not on the set-point real of pH 5.5 but on the corrected/artificial set point of 5.7. It should be noted that in a case where the speed of the feed pump=0, the input of controller 1 into controller 2 is also=0 as the value is multiplied (“×”). In such a case no disturbance of the feed pump has to be counteracted and controller 2 merely acts on any deviation between the set-point and the measured pH value.

[0142] FIG. 3

[0143] Specifically FIG. 3 shows that without the controller 1 (of FIG. 2, i.e. here controller PI) the controller 2 (of FIG. 2 i.e. here controller P) would constantly have to adjust whenever the feed pump conveying fluid flow into the conditioning volume is active in order to reach the pH setpoint as it has to take not on the altering pH levels but also the speed of the feed pump into account. Via employing also the controller 1 and especially the additional calculations leading to the correction factor (also termed corrected/artificial setpoint) thereby automatically setting the artificial setpoint the gap between the pH setpoint and the actuating pH value calculated by the controller 2 is automatically and reliably closed.

[0144] FIG. 4 is a schematic illustration of a combination of feedforward regulation and feedback control influencing the bleed pump. The feedforward component in this example is the speed of the feed pump conveying fluid flow into the feed and bleed unit operation and the feedback component is the detected UV value. The detected UV value corresponds to the least one feature related to the loading of the feed and bleed unit operation and is compared by the at least one process control system with a set point value. Additional calculations are performed by the process control system taking into account the deviation between said set point value and the actually detected UV value as well as the speed of the feed pump resulting in the actuating value for the bleed pump.

[0145] FIG. 5 is a schematic illustration of the method (1) described herein comprising a combination of feedforward regulation and feedback control influencing the bleed pump in a feed and bleed unit operation. In this specific example the feed and bleed unit operation is an ultrafiltration module (8). Prior to entering the ultrafiltration module (8) the product stream (2) , which in this example arrives from a previous unit operation enters a conditioning volume (3)—here a (conditioning) intermediate bag. The (conditioning) intermediate bag (3) comprises a weight sensor (4), here a scale, which measures the weight of the (conditioning) intermediate bag. Based on this measurement a weight feedback controller (5) of the process control system (PCS) can determine the fill level of the intermediate bag (3). If said fill level is above the set value the PCS will influence the corresponding actuator i.e. the speed of the pump conveying process stream from the (conditioning) intermediate bag into the ultrafiltration module (feed pump (11) will increase and vice versa.

[0146] In addition the unit operation comprises a UV detector (9) as sensor for loading of the feed and bleed unit operation. The recirculation rate of the fluid flow in this example is high enough so that the UV sensor (9) can be placed before, after or in parallel to the ultrafiltration module (8). Based on the signal transmitted by the UV detector, a UV feedback controller (7) of the process control system determines whether there is a deviation between the actual UV value and the set UV value. If there is a deviation, additional calculations are carried out by the process control system (symbolized by box (6)) via employing a combination of feedforward regulation and feedback control for influencing the bleed pump (12). In detail said deviation of is multiplied with the rate of the feed pump (11) conveying fluid flow from the (conditioning) intermediate bag to arrive at the actuating value that influences the bleed pump (12), i.e. the pump that pumps the ultrafiltrated product stream (10) out of the UV control loop and out of the ultrafiltration unit operation.

[0147] In other words the deviation between the actual UV value and the set UV value multiplied by the rate of the feed pump—e.g. the antibody concentration determined by UV detection (i.e. the concentration factor) multiplied by the flow rate—is the disturbance that has to be counteracted by the bleed pump, i.e. the pump that pumps the process stream out of the UV control loop. Thus, it was surprisingly found that instead of directly influencing the flow rate of the bleed pump a much tighter control is possible via using additional calculations to take into account the concentration factor when calculating the actuating value for the bleed pump. With this, only the concentration variations in the intermediate input need to be compensated, but variations in the feed flow rate are immediately compensated by taking into account the concentration factor when calculating the actuating value for the bleed pump.

[0148] FIG. 6 is a schematic illustration of the concept of synchronization of flow rates in a continuous production process in which different master units. Flow synchronization is required as it is not possible to control two master units with exactly equal flow rate. Therefore, at least one auxiliary stream must be present between two master units, which compensates the differences between the master unit flow rates. The auxiliary stream conveys liquid into the product stream or out of the product stream. The flow rates of the salve units are controlled by the process control system (PCS) via fill level and/or weight control of buffer volumes. In this example the buffer volume is provided in the form of surge bags.