Concentrated Diafiltration Buffer for Lower UF/DF Consumption
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Solution Overview
Problem
Current ultrafiltration/diafiltration (UF/DF) processes in biomanufacturing are resource-intensive, particularly in terms of diafiltration buffer consumption and batch preparation, especially when dealing with high-titer formulations.
Innovation Solution
The method involves using a diafiltration buffer concentrate diluted to 1:1 with water to reduce resource consumption, and employing an in-line dilution system for continuous and accurate dilution, ensuring precise diafiltration buffer preparation without the need for additional steps.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of substance
If traditional diafiltration buffer preparation methods are used, then complete buffer exchange is achieved, but diafiltration buffer consumption and batch preparation time increase significantly
Solution Approach 1:
The diafiltration buffer is pre-concentrated to a concentrate form before use. This preliminary concentration action reduces the total volume of buffer needed during the UF/DF process, thereby reducing buffer consumption and batch preparation time while maintaining the effectiveness of buffer exchange.
Solution Approach 2:
The buffer concentration parameter is changed from standard working concentration to a concentrated form (e.g., 2x or higher). This parameter change allows the same buffer to provide equivalent buffering capacity with reduced volume, directly addressing the contradiction between buffer consumption and process efficiency.
2Loss of time
If multiple diafiltration buffers are prepared separately, then buffer exchange is achieved, but process time and resource requirements increase
Solution Approach 1:
Multiple buffer preparation steps are merged into a single concentrate preparation step. Instead of preparing multiple separate diafiltration buffers, the system uses a single concentrated buffer that is diluted as needed, reducing both time and operational complexity.
Solution Approach 2:
The buffer preparation step is extracted from the main UF/DF process timeline. The concentrate is prepared in advance and stored, allowing the main process to proceed without waiting for buffer preparation, thereby reducing overall process time and simplifying operations.
3Measurement precision
If diafiltration buffer is diluted continuously, then dilution accuracy is improved, but system complexity increases
Solution Approach 1:
The in-line dilution system incorporates feedback mechanisms to monitor and adjust the dilution process. Sensors detect the actual concentration and provide feedback to control the dilution rate, ensuring accurate dilution ratios while maintaining system manageability through automated control.
Solution Approach 2:
Manual buffer preparation and dilution steps are replaced with an automated in-line dilution system. This substitution reduces human error in dilution accuracy while the automation manages the complexity through programmed control sequences and integrated pump 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
This approach reduces the resource requirements and time needed for UF/DF processes, maintaining process performance while minimizing diafiltration buffer batching, thus optimizing biomanufacturing efficiency.
Implementation Method 1
concentrating a first composition comprising a recombinant protein by ultrafiltration using the equilibrated UF/DF membrane filter
Implementation Method 2
diafiltering the first concentrated composition with the first diafiltration buffer to obtain a second composition
Data Source
AI summary
Disclosed herein are ultrafiltration/diafiltration (UF/DF) methods comprising the use of diafiltration buffer concentrates, as well as UF/DF methods in which a composition comprising a recombinant protein is concentrated by an ultrafiltration step to a recombinant protein concentration above an intended concentration following a subsequent diafiltration step.