Compensating Vessel Fill Level Control for Continuous Bioprocess
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Solution Overview
Problem
Current continuous downstream processes for biopharmaceutical production, such as virus inactivation and inline dilution, face challenges including prolonged process times, equipment complexity, and increased costs due to the use of intermediate containers, which can lead to product degradation and inefficient use of resources.
Innovation Solution
An electronic process control system adjusts the fill level in an expansion tank to maintain a continuous liquid flow by regulating the conveying arrangement, ensuring a predefined minimum or target fill level is maintained, thereby preventing interruptions and optimizing fluid delivery and mixing processes within the bioprocess arrangement.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If intermediate containers are used for virus inactivation and dilution processes, then virus inactivation can be performed, but process time is prolonged and product degradation risk increases
Solution Approach 1:
The patent implements continuous inline virus inactivation and dilution processes that eliminate batch processing interruptions. The system maintains continuous fluid flow through the bioprocess arrangement, allowing virus inactivation to occur continuously without stopping the upstream chromatography process. This continuous operation reduces total process time while maintaining effective virus inactivation through sustained exposure to inactivating agents.
Solution Approach 2:
The patent introduces intermediate fluid streams (such as acidified water for virus inactivation and neutralizing buffers) that act as mediators to enable continuous processing. These intermediary substances allow virus inactivation to occur inline without requiring physical intermediate containers, as the inactivation happens in-flow through controlled mixing and residence time management.
2Reliability
If intermediate containers are used for virus inactivation, then virus inactivation can be achieved, but equipment complexity increases
Solution Approach 1:
The patent merges the virus inactivation function with the existing continuous chromatography workflow by integrating inactivation steps inline. Instead of separate batch processing in intermediate containers, the system combines virus inactivation, dilution, and neutralization steps into a continuous inline process that occurs within the existing fluid delivery infrastructure, reducing the need for additional standalone equipment.
Solution Approach 2:
The patent designs the fluid delivery system to perform multiple functions: upstream chromatography eluate delivery, virus inactivation agent mixing, dilution, and neutralization. This multi-functional approach eliminates the need for dedicated intermediate containers for each step, as the same continuous flow system handles all operations, thereby reducing overall equipment complexity.
3Reliability
If intermediate containers are used for virus inactivation, then virus inactivation can be performed, but costs increase
Solution Approach 1:
The continuous inline processing eliminates the need for multiple batch processing cycles and associated intermediate container requirements. By maintaining continuous flow throughout virus inactivation and dilution, the system reduces consumable usage (buffers, solvents) and minimizes equipment footprint, leading to lower capital and operational costs while maintaining effective virus inactivation.
4Productivity
If continuous flow is maintained without intermediate containers, then process time is reduced and productivity increases, but control over fill level becomes critical
Solution Approach 1:
The patent implements electronic process control systems that monitor and adjust fluid delivery parameters in real-time. Sensors detect fill levels, flow rates, and other critical parameters, and the control system automatically adjusts pump speeds, valve positions, and mixing rates to maintain optimal conditions. This closed-loop feedback control ensures stable continuous operation without manual intervention, making the system easier to operate despite the critical nature of fill level control.
Data Source
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AI summary
The invention relates to a method for operating a continuous downstream process, in particular a continuous virus inactivation or inline dilution process, using a bioprocess arrangement (1), wherein the bioprocess arrangement (1) comprises a compensating vessel (2) with a first fluid inlet (3) configured for introducing a concentrate stream, in particular a product or buffer concentrate stream, into the compensating vessel (2), with at least a second fluid inlet (4) configured for introducing a diluter stream, in particular a product or buffer diluter stream, into the compensating vessel (2), with a fluid outlet (5) configured for discharging a fluid stream from the compensating vessel (2), wherein the bioprocess arrangement (1) comprises a conveying arrangement (6) for fluid conveying.the first fluid inlet (3) and the second fluid inlet (4) are each assigned to convey at least one fluid flow into the compensation tank (2), and the fluid outlet (5) is assigned to convey a fluid flow from the compensation tank (2), and wherein the bioprocess arrangement (1) has an electronic process control (7). It is proposed that the electronic process control (7) adjusts the fill level in the compensation tank (2) by controlling and/or regulating the conveying arrangement (6) such that a predefined minimum fill level in the compensation tank (2) is not undercut.