Research Background and Significance
In FMD vaccine production, cell culture supernatants contain a large amount of cell debris. If directly subjected to 0.2 μm sterilizing filtration, filter membranes are prone to rapid fouling, reducing efficiency and potentially affecting the permeability and yield of the target antigen (146S viral particles).
This study focuses on three key questions:
Comparing the performance of surface filtration and depth filtration in terms of throughput, turbidity reduction, and protection of downstream sterilizing filters.
Verifying the unique advantage of strong positively charged depth filters in cell debris removal.
Establishing scalable filtration schemes tailored to culture fluids with different turbidity levels, to meet industrial production needs.
Core Experiments and Results
Surface Filtration vs. Depth Filtration
Experiment: Inactivated FMD vaccine fluids were filtered using a 0.45 μm polypropylene surface membrane and depth filter sheets, followed by 0.2 μm sterilizing filtration.
Findings:
Starting turbidity: 77 NTU.
Depth filtration: throughput 641 L/m²; reduced turbidity to 9.65 NTU (clear and bright).
Surface filtration: throughput only 46 L/m²; turbidity remained 41 NTU.
Downstream sterilizing filtration: After depth filtration, 0.2 μm filters had a throughput of 655 L/m², compared with only 91 L/m² after surface filtration—a 7.2× improvement.
146S yield: Higher in depth filtration than in surface filtration.
Conclusion: Depth filtration throughput was 13.9× higher than surface filtration, filtrate turbidity was 76.5% lower, and sterilizing filter life was extended more than 7×. From both cost and yield perspectives, depth filtration is superior.
Positively Charged vs. Strongly Positively Charged Depth Filtration
Experiment: Two types of depth filter sheets with the same pore size but different charge density (normal positive vs. strong positive) were tested on inactivated FMD fluids.
Findings:
Throughput and pressure profiles were similar.
Normal positive depth filter: filtrate turbidity 25 NTU.
Strong positive depth filter: filtrate turbidity 9.65 NTU (only 38.6% of normal).
Strong charge capacity comes from special resin ligands that enhance electrostatic adsorption.
Literature reports confirm strong positive depth filters can also remove host cell proteins (HCP) and DNA.
Conclusion: Strong positive depth filters deliver significantly better turbidity reduction (<10 NTU), protect downstream ultrafiltration/sterilizing filtration, and remove additional process-related impurities.
1. Technical Principles and Advantages of Depth Filtration
Surface filtration: Captures particles only on the membrane surface; primarily size-based sieving.
Depth filtration: Removes particles throughout the matrix by both entrapment and electrostatic adsorption.
Key advantages:
No asbestos (unlike early filter media).
Made from high-purity cellulose fibers, filter aids, and polymeric resins.
Functional groups with positive charge provide strong adsorption for fine particles and impurities.
Fully compliant with biopharmaceutical regulatory requirements.
2. Scalable Filtration Schemes for Different Turbidity Levels
Based on comparative studies:
Low turbidity fluids: lighter pre-filtration sufficient.
Medium turbidity fluids: dual-layer depth filtration recommended.
High turbidity fluids: strong positive depth filtration required to reduce turbidity below 10 NTU, ensuring efficient downstream processing and high antigen yield.
3. Product Implementation: Great Wall Filtration Depth Filters
Great Wall Filtration offers depth filter systems designed for biopharmaceutical processes.
Key features:
High-capacity depth filter sheets for removal of cells, debris, and large solids.
Applicable to mammalian cell cultures, bacterial/yeast lysates.
Capable of removing HCP, DNA, viruses, endotoxins, and antifoaming agents.
Compact design, scalable linearly, suitable for in-line or parallel use.
Stable flow rates, long service life, and low operating cost.
Conclusion
Strong positively charged depth filtration technology significantly improves clarification efficiency and antigen recovery in FMD vaccine production. Beyond FMD vaccines, it provides a reliable pathway for purification in other biologics. As bioprocess optimization continues, advanced filtration technology will remain essential for safe and efficient vaccine manufacturing.
This article is based on real experimental data for reference only. Validation under actual production conditions is recommended.
