Two-Step Filtration for Virus Removal and Fouling Reduction
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Solution Overview
Problem
Current virus removal filtration methods in bioprocessing are prone to fouling, leading to increased costs, reduced product yield, and potential immunogenic reactions due to the presence of soluble protein aggregates and high molecular weight impurities, which are challenging to remove effectively using existing pre-filtration steps.
Innovation Solution
A two-step filtration method using a first filtration medium with a thickness of 5 to 20 μm and a second medium with a thickness of 20 to 70 μm, both with modal pore diameters in the range of 10 to 25 nm, significantly reduces fouling and extends the operational life of the second filtration medium by enhancing particle retention and throughput.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If size-exclusion filters are used for virus removal filtration, then virus removal efficiency is improved, but filter fouling increases leading to reduced operational life-time
Solution Approach 1:
The filtration process is divided into multiple sequential steps using different filter types: depth filtration (removing aggregates and impurities) followed by size-exclusion filtration (removing viruses). This segmentation prevents fouling of the size-exclusion filter by removing potential foulants beforehand, thereby extending its operational life while maintaining virus removal efficiency.
Solution Approach 2:
Depth filtration is performed as a preliminary step before size-exclusion filtration to remove protein aggregates, high molecular weight impurities, and other particulate matter. This preliminary action prevents these substances from reaching and fouling the size-exclusion filter, allowing it to operate at full efficiency for longer periods.
2Duration of action of stationary object
If pre-filtration steps using 0.1 to 0.2 μm membranes are used to remove aggregates, then filter fouling is reduced, but sub-0.1 μm impurities remain causing product contamination
Solution Approach 1:
Depth filtration media with specific pore size distributions are used to remove particles in the 0.01 to 0.1 μm range that would pass through conventional 0.1 to 0.2 μm membranes. The porous structure of the depth filtration media allows effective removal of these smaller impurities while maintaining high throughput and preventing fouling of subsequent size-exclusion filters.
3Reliability
If virus removal filters with narrow pore size distributions are used, then virus removal efficiency is improved, but manufacturing cost increases significantly
Solution Approach 1:
The filtration system is segmented into depth filtration and size-exclusion filtration stages. The depth filtration stage uses more cost-effective media to remove aggregates and impurities, while the size-exclusion filter operates at optimal performance for virus removal. This segmentation reduces the overall cost while maintaining high virus removal efficiency.
Solution Approach 2:
Depth filtration media are used as disposable pre-filters that can be replaced easily and at lower cost. These media handle the fouling burden, protecting the more expensive size-exclusion filters from contamination and extending their usable life, thereby reducing overall manufacturing costs.
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 increases product yield, reduces filter fouling, and enhances virus removal efficiency, leading to lower costs and reduced immunogenic impurities, while maintaining the integrity of the biological sample.
Implementation Method 1
passing the feed fluid through a first filtration medium having a thickness of from 5 to 20 μm, wherein passing the feed fluid through the first filtration medium provides a particle removal probability log10 reduction value (LRV) of greater than or equal to 1 for particles having a diameter of below or equal to about 40 nm and a particle removal probability log reduction log10 reduction value (LRV) of greater than or equal to 3 for particles greater than, or equal to, about 40 nm in diameter
Implementation Method 2
passing the fluid through a second filtration medium having a thickness of from 20 to 70 μm (e.g. 20 to 45 μm), wherein passing the feed fluid through the second filtration medium provides a particle removal probability log10 reduction value (LRV) of greater than or equal to 3 for particles having a diameter of from about 10 to about 40 nm and a particle removal probability log reduction value (LRV) of greater than or equal to 3 for particles having a diameter of greater than, or equal to, about 40 nm
Data Source
AI summary
The present invention provides method of removing particles from a feed fluid, the method comprising: passing the fluid through a first filtration medium having a thickness of from 5 to 20 μm, wherein passing the feed fluid through the first filtration medium provides a particle removal probability log10 reduction value (LRV) of greater than or equal to 1 for particles having a diameter of from about 10 to about 40 nm and a particle removal probability log10 reduction value (LRV) of greater than or equal to 3 for particles greater than about 40 nm in diameter; and passing the fluid through a second filtration medium having a thickness of from 20 to 70 μm (e.g. 20 to 45 μm) 20 to 45 pm, wherein passing the feed fluid through the second filtration medium provides a particle removal probability log10 reduction value (LRV) of greater than or equal to 3 for particles having a diameter of from about 10 to about 40 nm and a particle removal probability log10 reduction value (LRV) of greater than or equal to 3 for particles having a diameter of greater than or equal to about 40 nm; so as to retain at least a portion of the particles on each medium to produce a filtrate containing a lower concentration of the particles than the feed fluid.