Viral Inactivation via pH Control in Polypeptide Mixtures
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for viral inactivation in polypeptide mixtures are inefficient and prone to error, often requiring trial and error approaches that result in high costs and long processing times, especially in commercial-scale drug product synthesis, where achieving a precise pH for viral inactivation is challenging.
Innovation Solution
A method involving the calculation and controlled addition of acid to achieve a pH between 3.0 and 3.8 for a specified interval to inactivate viruses, using chromatography and mathematical models to determine the exact acid amount based on protein concentration and pH measurements, ensuring effective viral inactivation without denaturing target molecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If trial and error approaches are used for viral inactivation, then viral reduction can be achieved, but processing time increases and costs increase
Solution Approach 1:
The patent applies preliminary action by pre-determining the exact amount of acid to add based on mathematical models that incorporate real-time pH and protein concentration measurements. This eliminates the need for trial-and-error approaches during the actual viral inactivation process, reducing processing time while maintaining effectiveness.
Solution Approach 2:
The patent implements feedback through continuous monitoring of pH and protein concentration during the process. These real-time measurements are fed into mathematical models that calculate the precise acid addition amount, creating a closed-loop control system that ensures reliable viral inactivation without time-consuming iterations.
2Reliability
If trial and error approaches are used for viral inactivation, then viral reduction can be achieved, but manufacturing costs increase
Solution Approach 1:
The patent uses feedback from real-time pH and protein concentration measurements to calculate the precise acid addition amount through mathematical models. This eliminates wasteful trial-and-error acid additions, reducing material costs and improving manufacturing efficiency while ensuring reliable viral inactivation.
Solution Approach 2:
The patent applies parameter changes by using mathematical models that dynamically adjust the acid addition calculation based on real-time measurements of pH and protein concentration. This optimized parameter control reduces acid consumption and processing steps, lowering manufacturing costs while maintaining viral inactivation effectiveness.
3Reliability
If acid is added to achieve target pH for viral inactivation, then viral reduction is achieved, but risk of denaturing target polypeptide increases
Solution Approach 1:
The patent applies parameter changes by using mathematical models that precisely calculate the acid addition amount based on real-time pH and protein concentration measurements. This precise control ensures the pH reaches the inactivation range (3.0-3.8) without excessive acid addition that could denature the target polypeptide, maintaining both viral inactivation effectiveness and polypeptide stability.
Solution Approach 2:
The patent replaces the mechanical trial-and-error approach with a computational system using mathematical models and real-time sensor data. This substitution enables precise prediction of the acid addition amount, ensuring the pH reaches the optimal inactivation range without overshooting and causing polypeptide denaturation.
4Productivity
If precise pH control is implemented for viral inactivation, then process efficiency improves, but measurement and control complexity increases
Solution Approach 1:
The patent applies universality by using a single integrated mathematical model that simultaneously processes pH and protein concentration measurements to calculate acid addition amount. This multi-functional approach consolidates multiple measurement and control functions into one unified system, improving process efficiency without proportionally increasing complexity.
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 significantly reduces viral activity, achieving a viral reduction factor of at least 2.5, enhances process efficiency, and ensures product stability and safety by providing a precise and reproducible method for viral inactivation in polypeptide mixtures.
Implementation Method 1
an amount of acid necessary to reduce the pH of the mixture to an inactivation pH may then be calculated based on the protein concentration of the mixture
Implementation Method 2
Separation processes such as, for example, affinity chromatography and the like, may be performed as a part of target molecule preparation processes
Data Source
AI summary
Embodiments of the present disclosure are directed to systems and methods for modulating pH in a mixture containing a polypeptide. The pH may be modulated for any suitable purpose, e.g., inactivating virus in the mixture. Methods may include eluting, from a chromatography column, a mixture (e.g., an eluate) having a pH greater than, e.g., 3.9 and less than, e.g., 8.5. Methods may further include one or more of measuring a protein concentration of the mixture and measuring a pH of the mixture. An amount of acid necessary to reduce the pH of the mixture to a target pH may then be calculated based on the protein concentration of the mixture, the pH of the mixture, or both. After an acid addition amount is calculated, a portion of acid may be added to the mixture, wherein the portion of acid is sufficient to achieve the target pH.