Continuous Monoclonal Antibody Purification with In-Line pH Control
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Solution Overview
Problem
Current downstream purification processes for monoclonal antibodies require multiple batch operations and intermediate holding tanks for pH and conductivity adjustments, leading to increased processing time and costs, and lack automation for real-time parameter adjustments.
Innovation Solution
A continuous separation system with in-line sensing and adjustment means between chromatography and filtration steps, allowing for real-time monitoring and control of environmental parameters such as pH, conductivity, and protein concentration, eliminating the need for intermediate holding tanks and enabling automated, high-throughput processing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If batch processes with intermediate holding tanks are used for pH and conductivity adjustments between chromatography steps, then separation purity is maintained, but processing time and operational complexity increase
Solution Approach 1:
The patent implements continuous in-line adjustment of pH and conductivity parameters between chromatography steps, eliminating the discontinuous batch processing with intermediate holding tanks. The system continuously monitors and adjusts fluid parameters as they flow through the system, maintaining separation purity while reducing processing time by eliminating idle holding periods and intermediate transfer operations.
Solution Approach 2:
The patent introduces in-line adjustment units as intermediary components between chromatography steps. These units act as mediators that continuously modify fluid properties (pH, conductivity) directly in the flow path, replacing the traditional batch-wise adjustment process that required intermediate holding tanks and manual intervention.
2Manufacturing precision
If multiple intermediate batch operations are performed for parameter adjustments, then optimal separation conditions are achieved, but device complexity and operational steps increase
Solution Approach 1:
The patent combines multiple separate batch adjustment operations into a single integrated in-line adjustment unit. Instead of performing pH adjustment, conductivity adjustment, and holding in separate batch steps with intermediate transfers, the system merges these functions into continuous in-line operations that occur as fluid flows through the chromatography system, reducing device complexity while maintaining control precision.
Solution Approach 2:
The in-line adjustment units are designed to perform multiple functions simultaneously - adjusting pH, adjusting conductivity, and preparing fluid for the next chromatography step - all within a single continuous operation. This multi-functionality replaces the need for multiple specialized batch operations and intermediate holding tanks, simplifying the overall system architecture.
3Manufacturing precision
If Protein A affinity chromatography is used for capture, then high purification efficiency is achieved, but protein leakage and process complexity occur
Solution Approach 1:
The patent employs in-line adjustment of critical parameters (pH, conductivity) between chromatography steps to optimize separation conditions and minimize protein leakage. By continuously adjusting these parameters to optimal values for each specific chromatography step, the system maintains high purification efficiency while reducing the harmful effects of protein leakage that occur with fixed-parameter batch processes.
4Productivity
If automated in-line adjustment is implemented, then processing speed and throughput increase, but measurement and control requirements become more stringent
Solution Approach 1:
The patent implements automated feedback control systems that continuously monitor fluid parameters (pH, conductivity) and automatically adjust them in real-time. The system measures actual parameter values, compares them to target values, and makes automatic adjustments to maintain optimal conditions, thereby enabling high throughput while ensuring measurement and control accuracy through closed-loop feedback mechanisms.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach reduces processing time and costs, enhances manufacturing efficiency, and ensures high accuracy and reproducibility by maintaining optimal separation conditions, thereby improving the overall downstream purification process for monoclonal antibodies.
Implementation Method 1
The feed stream is passed over a cation exchange chromatography column and monoclonal antibodies are captured
Implementation Method 2
The eluate from the cation exchange column is then passed over an anion exchange column
Implementation Method 3
The eluate from the anion exchange column is then passed through a tangential flow filtration system to remove virus particles
Data Source
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AI summary
A separation system comprises (i) at least two separation units, each separation unit comprising a fluid inlet and a fluid outlet, wherein the separation units are connected in series outlet to inlet to form a line of separation units, and (ii) sensing and adjustment means, provided in-line between each separation unit, for continuously monitoring and adjusting at least one environmental property parameter of fluid flowing from one separation unit to a subsequent separation unit in the line of separation units. Uses of the separation system and a method for purification of a liquid containing a desired species, using separation units and in-line adjustment of a fluid flow or flows, are also disclosed.