Continuous Perfusion Filter for Haemostasis Protein Production
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Solution Overview
Problem
Current processes for producing haemostasis proteins, such as Factor VII, Factor VIII, and Factor IX, face challenges in achieving high yields without compromising product quality, particularly in scaling up from lab to large-scale fermentations.
Innovation Solution
A continuous perfusion culturing process using a filter module with a mesh size of 0.1 to 2.9 μm, employing alternating tangential flow, which allows the passage of haemostasis proteins while retaining cells and cell debris, thereby enabling higher titre production without compromising growth or productivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If continuous perfusion culturing is used with a filter module, then protein yield increases significantly, but cell retention and product quality must be maintained
Solution Approach 1:
The filter module employs a porous structure with mesh size of 0.1 to 2.9 μm that allows passage of haemostasis proteins while retaining cells and cell debris. The porous material enables selective separation based on size, achieving high protein yield while maintaining product quality through consistent filtration performance.
Solution Approach 2:
The system utilizes alternating tangential flow (ATF) through the filter module, creating hydraulic conditions that enhance protein passage while maintaining cell retention. The alternating flow pattern prevents clogging and maintains consistent filtration efficiency, enabling high productivity without compromising product quality.
2Quantity of substance
If mesh size is reduced to retain more cells, then cell retention improves, but protein passage may be hindered
Solution Approach 1:
The filter module mesh size is optimized within the range of 0.1 to 2.9 μm, representing a specific parameter change that balances cell retention and protein passage. This parameter optimization ensures sufficient cell retention while maintaining adequate protein productivity, resolving the contradiction between quantity of substance and productivity.
3Productivity
If alternating tangential flow is applied, then protein passage is enhanced, but process complexity increases
Solution Approach 1:
The system employs alternating tangential flow where the flow direction alternates periodically through the filter module. This periodic action enhances protein passage by preventing accumulation and clogging, while the alternating pattern maintains relatively simple device architecture compared to continuous complex control 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 process achieves significantly higher protein yields, up to ten times greater than prior methods, while maintaining high product quality and cell viability, across various scales from lab to large-scale fermentations.
Implementation Method 1
the filter module having a mesh size of from 0.1 to 2.9 μm allowing passage across of the haemostasis protein
Implementation Method 2
the flow across the filter module is an alternating tangential flow
Data Source
AI summary
The present invention relates to a process for the production of a haemostasis protein by continuous perfusion culturing of a cell culture in suspension, said cell culture expressing said haemostasis protein into said culture suspension, wherein the cell culture flows across a filter module, which filter module leads to a harvest port, the filter module having a mesh size of from 0.1 to 2.9 μm allowing passage across of the haemostasis protein and wherein the flow across the filter module is an alternating tangential flow. The invention also relates to a protein produced by the process of the invention.