Virus Filtration Using Diafiltrate Buffer to Reduce Plugging
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Solution Overview
Problem
The existing purification processes for biomolecules, such as therapeutic antibodies, face challenges with filter plugging during virus filtration due to the retention of high molecular weight impurities and protein aggregates, leading to increased processing costs and reduced throughput.
Innovation Solution
The method involves performing virus filtration using a diafiltrate buffer, which is the same as the final product formulation buffer, and includes a diafiltration step directly before virus filtration to reduce filter plugging and maintain product stability, allowing for higher throughputs and more efficient manufacturing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If virus filtration is performed using conventional buffers, then virus removal is achieved, but filter plugging occurs due to retention of high molecular weight impurities and protein aggregates
Solution Approach 1:
The patent applies preliminary action by performing a diafiltration step before virus filtration to remove high molecular weight impurities and protein aggregates from the feed stream. This pre-treatment prevents these contaminants from reaching and plugging the virus filtration membrane, thereby maintaining filter throughput while ensuring effective virus removal
Solution Approach 2:
The patent uses an intermediary approach by introducing a diafiltration step as a mediator between the chromatography process and virus filtration. This intermediate step acts as a protective barrier that removes interfering substances without compromising the subsequent virus filtration effectiveness
2Productivity
If filter area is increased to maintain throughput, then virus filtration capacity is improved, but processing cost and time increase
Solution Approach 1:
By performing diafiltration before virus filtration to remove aggregates and high molecular weight impurities, the patent enables the use of smaller filter areas while maintaining required throughput. The pre-treatment ensures that fewer filters are needed to achieve the same processing capacity, thereby reducing processing time and costs
3Device complexity
If conventional buffers are used in filtration, then process simplicity is maintained, but product stability may be compromised
Solution Approach 1:
The patent applies parameter changes by using formulation buffers (with specific pH, conductivity, and composition matching the final product) instead of conventional filtration buffers. This parameter optimization maintains product stability during filtration while the diafiltration step ensures efficient buffer exchange, achieving both stability and process effectiveness
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 virus filtration area, enabling higher concentration processing and more efficient production of biomolecules like monoclonal antibodies with improved stability and cost-effectiveness.
Implementation Method 1
virus filtration can be carried out using a diafiltrate buffer
Implementation Method 2
subjecting the sample to ultrafiltration with a tangential flow filtration (TFF) unit equipped with an ultrafiltration membrane
Data Source
AI summary
Method and system for purifying a sample comprising a biomolecule of interest and impurities, comprising expressing said biomolecule of interest in a bioreactor to form a product sample comprising said biomolecule of interest and impurities; subjecting said product sample to filtration to form a clarified product sample; subjecting said clarified product sample to affinity chromatography to remove impurities; subsequently subjecting said product sample to diafiltration followed by virus filtration and optional concentration. The buffer used during the diafiltration step (and thus in the virus filtration step) is the buffer desired for the final formulation of the product.