Virus Removal Membrane Filtration pH Salt Ionic Strength Control
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Solution Overview
Problem
Conventional filtration of protein solutions using small-pore size virus removal membranes at high pressures is inefficient, leading to potential virus leakage into filtrates and reduced virus removal rates, especially at low filtration pressures during post-wash or stop-and-start steps.
Innovation Solution
Adjusting the pH and salt ionic strength of the solution to specific values before filtration through a small-pore size virus removal membrane, allowing for effective virus removal at low filtration pressures by ensuring the solution conditions satisfy certain equations, thereby preventing virus leakage and achieving high virus removal rates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If filtration is carried out at high pressure to increase throughput, then productivity is improved, but virus removal rate deteriorates due to virus leakage into filtrates
Solution Approach 1:
The invention changes the physical-chemical parameters of the protein solution (pH and salt ionic strength) to specific ranges before filtration. By controlling pH within 3.5-8.0 and salt ionic strength within 0.05-0.5, the virus removal rate is maintained at 4 log or higher even at low filtration pressures, preventing virus leakage while ensuring productivity
2Stability of the object's composition
If filtration pressure is decreased to prevent protein denaturation and maintain protein activity, then protein stability is improved, but virus removal rate deteriorates due to increased virus permeation
Solution Approach 1:
The invention adjusts the pH and salt ionic strength parameters of the solution to specific ranges that enable effective virus removal at low filtration pressures. This allows the filtration to be performed at pressures that do not denature proteins while still achieving the required virus removal rate of 4 log or higher
3Productivity
If high-concentration protein solutions are filtered to meet demand for higher protein concentrations, then productivity is improved, but filtration clogging increases due to protein accumulation in membrane pores
Solution Approach 1:
The invention modifies the solution parameters (pH and salt ionic strength) to optimize filtration characteristics. By controlling pH within 3.5-8.0 and salt ionic strength within 0.05-0.5, the membrane pores remain more open to protein molecules, reducing clogging even when filtering high-concentration solutions, thus maintaining both productivity and filtration efficiency
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
The method ensures a high rate of virus removal, as demonstrated by log reduction values of 4 or higher, even at low filtration pressures, effectively preventing virus contamination in protein drugs.
Implementation Method 1
the viruses are separated and removed by filtration using virus removal membranes as physical virus removal means
Implementation Method 2
a filtration step of filtering a virus-containing protein solution through a small-pore size virus removal membrane, wherein the small-pore size virus removal membrane has a pore size that does not permit permeation of viruses but permits permeation of protein molecules
Data Source
Figure 1
AI summary
The present invention provides a method for manufacturing a virus-free protein drug, comprising (a) a filtration step of filtering a virus-containing protein solution through a small-pore size virus removal membrane to obtain a virus-free protein solution, the filtration step (a) comprising (q) a low-pressure filtration step of filtering the solution through the small-pore size virus removal membrane at a filtration pressure of 0.30 kgf/cm2 or lower to obtain the virus-free protein solution, wherein the solution prior to filtration in the low-pressure filtration step (q) has a pH (X) and a salt ionic strength (Y (mM)) that satisfy the following equations 1 and 5: 0 ≤ Y ≤ 150X - 590 (Equation 1) and 3.5 ≤ X ≤ 8.0 (Equation 5) or the following equations 4 and 5: Y = 0 (Equation 4) and 3.5 ≤ X ≤ 8.0 (Equation 5).