Two-Stage Ultrafiltration for High-Concentration IgG
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for concentrating plasma products using ultrafiltration membranes face challenges with high viscosity and protein concentration, leading to reduced yield and membrane fouling, making it difficult to achieve high final concentrations without significant yield loss and increased processing time.
Innovation Solution
A two-stage ultrafiltration/diafiltration method involving a first membrane for initial concentration, diafiltration with an aqueous solution, formulation with glycine, and pH adjustment, followed by a second ultrafiltration stage using a membrane with twice the molecular weight cutoff of the first, to achieve higher final concentrations of plasma products like IgG.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If a single ultrafiltration membrane is used to achieve high final concentrations, then the concentration of plasma products is increased, but yield loss increases and membrane fouling occurs
Solution Approach 1:
The ultrafiltration process is divided into two sequential stages using membranes with different molecular weight cutoffs. The first stage uses a membrane with a lower MWCO (e.g., 50 kDa) to concentrate to an intermediate concentration (e.g., 5-10%), while the second stage uses a membrane with a higher MWCO (e.g., 100 kDa or 200 kDa) to achieve the final high concentration (e.g., 20-50%). This segmentation prevents the single membrane from operating under excessively harsh conditions that cause fouling and yield loss.
Solution Approach 2:
The process changes the operating parameters by using different molecular weight cutoffs at different concentration stages. The first membrane operates at lower concentration conditions with a tighter cutoff, while the second membrane operates at higher concentration conditions with a looser cutoff. This parameter change allows each membrane to operate in its optimal performance range, avoiding the fouling and yield loss problems associated with using a single membrane for the entire concentration range.
2Quantity of substance
If high final concentrations are targeted, then the concentration of plasma products is increased, but processing time increases
Solution Approach 1:
The concentration process is segmented into two stages, each operating at different concentration levels. The first stage rapidly concentrates to an intermediate level where the membrane operates efficiently with lower viscosity. The second stage then completes the concentration to the final high level. This segmentation avoids the time penalty of attempting to concentrate directly to high levels in a single stage, where viscosity increases would slow down the process.
Solution Approach 2:
By changing the molecular weight cutoff parameter between stages, the process optimizes the concentration rate at each level. The first membrane with lower MWCO provides efficient initial concentration, and the second membrane with higher MWCO completes the process. This parameter change strategy reduces overall processing time compared to using a single membrane throughout the entire concentration range.
3Quantity of substance
If a single ultrafiltration membrane is used to achieve high final concentrations, then the concentration of plasma products is increased, but membrane fouling increases
Solution Approach 1:
The fouling problem is addressed by segmenting the concentration process into two stages with different membranes. The first membrane operates at lower concentration conditions where fouling is minimized, and the second membrane handles the final high-concentration step. This segmentation prevents any single membrane from being exposed to the full severity of high-concentration fouling conditions throughout the entire process.
Solution Approach 2:
The process changes the molecular weight cutoff parameter between stages to optimize membrane performance and minimize fouling. The first membrane with lower MWCO operates at conditions that reduce fouling, and the second membrane with higher MWCO completes the concentration. This parameter change strategy allows each membrane to operate in a regime that minimizes fouling while achieving the desired final concentration.
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 effectively increases the concentration of plasma products while minimizing yield loss and processing time, enabling the production of high-concentration formulations suitable for therapeutic use without significant membrane fouling.
Implementation Method 1
a) ultrafiltering the solution using a first membrane to form a first retentate solution comprising the protein at a first concentration, wherein the first membrane has a molecular weight cutoff sufficient to retain at least a portion of the protein present in the solution
Implementation Method 2
d) ultrafiltering the second retentate solution using a second membrane to form a final retentate solution comprising the protein at a second concentration, wherein the second membrane has a molecular weight cutoff of about twice the molecular weight cutoff of the first membrane
Data Source
AI summary
The present invention provides a method for concentrating a protein, in particular a method for concentrating a plasma product, in particular IgG, using glycine in a two-stage ultrafiltration/diafiltration approach.