Pre-filtration Buffer Adjustment for Immunoglobulin TFF Stability
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Solution Overview
Problem
Tangential flow filtration processes for immunoglobulin concentration face challenges in maintaining predefined solute concentrations and pH values due to thermodynamic non-ideality and unequal partitioning of solutes during ultrafiltration, leading to variations in conductivity and stability issues in the final product.
Innovation Solution
An ultrafiltration method involving pre-filtration solute concentration adjustment using equations 2 and 3 to calculate the necessary buffer substance concentration, maintaining the pH value, and subsequent tangential flow filtration to achieve defined solute concentrations, thereby correcting for changes in conductivity and pH during the concentration process.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If tangential flow filtration is used for immunoglobulin concentration, then concentration speed is improved, but solute concentration and pH values deviate from predefined values due to thermodynamic non-ideality and unequal partitioning
Solution Approach 1:
The patent applies preliminary action by calculating and adjusting the initial solute concentration before ultrafiltration based on equations that account for thermodynamic non-ideality. The method pre-determines the required buffer substance concentration and pH adjustment to compensate for expected deviations during concentration, ensuring final product meets specifications without requiring post-process adjustments.
Solution Approach 2:
The patent employs parameter changes by dynamically adjusting multiple parameters including initial solute concentration, pH value, and buffer substance composition before ultrafiltration. These parameter modifications are calculated using specific equations that relate protein concentration, charge, and solute partitioning behavior to predict and correct for non-ideal thermodynamic effects during the concentration process.
2Productivity
If tangential flow filtration is used for immunoglobulin concentration, then productivity is improved, but conductivity and pH values vary leading to stability issues
Solution Approach 1:
The method performs preliminary calculations of required buffer substance concentration and pH adjustment before ultrafiltration begins. By pre-determining these parameters based on the specific protein and solute system, the process ensures that conductivity and pH remain within stable ranges throughout concentration, preventing stability issues while maintaining high productivity.
Solution Approach 2:
The patent incorporates feedback mechanisms through monitoring of conductivity and pH during ultrafiltration, with calculations that continuously account for changing solute concentrations. This feedback allows for real-time adjustment of process parameters to maintain product stability while preserving high throughput capability.
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 method ensures consistent solute concentrations and pH values, maintaining the stability of immunoglobulin solutions and preventing aggregate formation, while maintaining the transmembrane flux and concentration time, thus producing high-quality concentrated immunoglobulin preparations.
Implementation Method 1
tangential flow filtration (TFF) processes are used
Implementation Method 2
a tangential flow filtration (TFF) process with a pre-filtration solute concentration adjustment
Implementation Method 3
the ratio between buffer anion/buffer cation and buffer acid is calculated for each pH value determined in the retentate by using the Henderson-Hasselbach-Equation
Implementation Method 4
Thermodynamic non-ideality of protein containing solutions during membrane based processes has been reported
Implementation Method 5
unequal partitioning of solutes during ultrafiltration
Data Source
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AI summary
Herein is reported a tangential flow filtration method with a pre-filtration solute concentration adjustment in order to ensure a defined concentration of the components of the solution after tangential flow filtration.