Continuous Virus Inactivation in Protein Manufacturing With Fixed Ratios
Solution Overview
Problem
Existing methods for inactivating viruses during protein manufacture are inefficient and unstable due to reliance on batch processes, pH feedback loops, and uncontrolled fluctuations, which prolong processing times and compromise the quality of biopharmaceutical products.
Innovation Solution
A method involving a single predetermined volumetric ratio for combining protein and virus-inactivation reagents, followed by continuous transfer and incubation in a treatment vessel without feedback control, ensures consistent virus inactivation across varying protein concentrations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If batch mode processing with pH feedback control is used for virus inactivation, then virus inactivation can be accomplished, but processing time is substantially prolonged and process stability is compromised
Solution Approach 1:
The patent implements continuous processing where the protein solution flows continuously through the treatment vessel with continuous addition of virus-inactivation reagent, eliminating the batch mode stop-start operations. This continuous flow approach maintains constant virus inactivation action throughout the process, reducing processing time while ensuring reliable virus inactivation through sustained exposure to inactivating conditions.
Solution Approach 2:
The patent establishes predetermined volumetric ratios for combining protein solution and virus-inactivation reagent before the actual inactivation process begins. These pre-determined ratios are based on predicted protein concentration ranges, allowing the system to operate without real-time feedback control adjustments, thereby reducing processing time while maintaining effective virus inactivation through pre-planned optimal conditions.
2Reliability
If pH feedback control with multiple adjustment steps is used, then virus inactivation can be achieved, but process complexity increases and stability decreases due to uncontrolled fluctuations
Solution Approach 1:
The patent removes the pH feedback control mechanism and multiple adjustment steps from the virus inactivation process. By extracting this complex control system, the process becomes simpler and more stable, while virus inactivation effectiveness is maintained through continuous processing and predetermined volumetric ratios that ensure adequate reagent addition without requiring real-time pH monitoring and adjustment.
Solution Approach 2:
The system uses predetermined volumetric ratios that are selected to ensure the predetermined property (virus inactivation effectiveness) is maintained across a range of predicted protein concentrations. This self-regulating approach eliminates the need for external feedback control, reducing process complexity while maintaining reliability through built-in robustness to concentration variations.
3Reliability
If batch mode with extended incubation times is used, then complete virus inactivation is achieved, but productivity decreases due to composition idle time
Solution Approach 1:
The patent implements continuous processing where protein solution flows constantly through the treatment vessel, eliminating idle incubation time. The virus inactivation action continues uninterrupted as the solution flows through the vessel under controlled conditions, achieving complete inactivation while maintaining high productivity through continuous throughput rather than batch-wise processing with downtime.
4Reliability
If feedback control with volumetric ratio adjustment is implemented, then virus inactivation can be optimized, but process stability is reduced due to susceptibility to fluctuations
Solution Approach 1:
The patent establishes predetermined volumetric ratios for combining protein solution and virus-inactivation reagent before the actual inactivation process begins. These pre-determined ratios are based on predicted protein concentration ranges, allowing the system to operate without real-time feedback control adjustments. This preliminary planning approach reduces susceptibility to fluctuations and maintains process stability while ensuring effective virus inactivation through robust pre-planned conditions.
Solution Approach 2:
The system uses predetermined volumetric ratios that are selected to ensure the predetermined property (virus inactivation effectiveness) is maintained across a range of predicted protein concentrations. This self-regulating approach eliminates the need for external feedback control, reducing process stability issues associated with fluctuating adjustments while maintaining reliable virus inactivation through built-in robustness to concentration variations.
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 stabilizes virus inactivation, eliminating the need for feedback control and reducing processing time, thereby ensuring the quality and safety of biopharmaceutical products.
Implementation Method 1
combining, at a single predetermined volumetric ratio, a composition including the protein, and a composition including a virus-inactivation reagent, to obtain a treatment composition having a predetermined property for inactivation of a virus
Implementation Method 2
incubating the treatment composition in the treatment vessel at predetermined conditions
Data Source
AI summary
Methods for continuously inactivating a virus during manufacture of a protein are provided. Steps include (1) combining, at a single predetermined volumetric ratio, a composition including the protein, and a composition including a virus-inactivation reagent, to obtain a treatment composition having a predetermined property for inactivation of a virus; (2) transferring the treatment composition to a treatment vessel; (3) incubating the treatment composition in the treatment vessel at predetermined conditions; and (4) subjecting the treatment composition to a post-treatment processing operation. The single predetermined volumetric ratio has been selected to ensure that the predetermined property of the treatment composition is maintained across a range of concentrations predicted for the protein in the composition including the protein. Steps (1) to (3) are carried out (a) continuously and (b) without feedback control being exerted by either adjustment of the volumetric ratio or diversion of the treatment composition.