Continuous Viral Clearance Testing With Controlled Virus Spiking
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Solution Overview
Problem
Existing viral clearance tests are not suitable for continuous processes, lacking reproducibility and accuracy in evaluating viral clearance capacity.
Innovation Solution
A method involving controlled flow rates and continuous supply of protein and virus solutions through a protein purification unit and virus removal filter, with specific rate calculations and measurements to determine viral clearance capacity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If a viral clearance test is performed using conventional batch processing methods, then the test can be conducted with simple equipment and操作流程, but the test cannot be applied to continuous processes and lacks reproducibility
Solution Approach 1:
The continuous viral clearance test system is segmented into distinct functional modules: a protein purification unit for continuous protein processing, a virus spiking system for controlled virus addition, and a virus removal filter for continuous filtration. Each module operates independently but connects to form a continuous flow system, enabling the test to be applied to continuous processes while maintaining manageable complexity through modular design
Solution Approach 2:
The system maintains continuous flow of protein solution through the purification unit and continuous spiking of virus solution at controlled rates. The continuous operation eliminates batch processing interruptions, enabling the test to evaluate viral clearance capacity under continuous process conditions that reflect actual manufacturing scenarios
2Measurement precision
If virus solution is added at variable rates, then the mixing process becomes more flexible, but the viral clearance measurement loses reproducibility and accuracy
Solution Approach 1:
The system incorporates flow rate monitoring and control mechanisms that provide feedback to maintain constant virus solution spiking rates. This feedback control ensures that the mixing ratio between protein solution and virus solution remains consistent, thereby achieving reproducible and accurate viral clearance measurements while still allowing operational adjustments within controlled parameters
Solution Approach 2:
The system controls the spiking rate of virus solution as a critical parameter, maintaining it at a constant value to ensure measurement reproducibility. By fixing this parameter while allowing other operational parameters to be adjusted, the system achieves both measurement precision and operational flexibility
3Measurement precision
If the virus concentration in the mixture is not controlled, then the spiking process becomes simpler, but the log reduction value calculation becomes inaccurate
Solution Approach 1:
The system performs preliminary preparation of virus solution with precisely controlled concentration before the actual spiking process. By pre-establishing the virus concentration and preparing standardized virus stocks, the system ensures accurate log reduction value calculation without requiring complex real-time concentration control during the spiking process
Solution Approach 2:
The system uses a standardized virus solution with known concentration as a reference template for all spiking operations. This standardized virus stock serves as a copyable reference that ensures consistent virus concentration across different experiments, thereby achieving accurate log reduction measurements without complex concentration control systems
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
Enables reproducible and accurate viral clearance testing in continuous processes, ensuring high viral removal efficiency and consistent log reduction values.
Implementation Method 1
a virus removal filter
Data Source
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AI summary
The purpose of the present invention is to provide a viral clearance test method, including supplying a protein solution to a first channel 10 provided with, upstream and downstream thereof, a protein purification unit 11 and a virus removal filter 12, respectively, and pouring the protein solution into the protein purification unit 11 at a first constant rate; supplying, at a second constant rate, a virus solution to a second channel 20 connected between the protein purification unit 11 and the virus removal filter 12 in the first channel and mixing the purified protein solution with the virus solution in the first channel 10; pouring the mixture of the protein solution and the virus solution into the virus removal filter 12 at a third constant rate; and measuring a virus contained in the permeate of the mixture which has passed through the virus removal filter 12.