The imperative task of ensuring product safety and efficacy within the realms of biopharmaceutical and biotechnological processes revolves primarily around the purification and eradication of viruses. Viruses, clandestine in their potential harm, cast substantial threats not only upon patients but also upon the integrity of the manufacturing process itself.
In response to this formidable challenge, chromatography processes have emerged as a stalwart solution, employing a diverse array of techniques and adsorbents to execute the pivotal role of virus purification and elimination. In this discourse, we embark upon a comprehensive exploration of the pivotal contributions of polysaccharide adsorbents, particulate resins, and membrane adsorbers within the domain of virus purification and removal chromatography processes.
Polysaccharide Adsorbents
Polysaccharide-based adsorbents have emerged as highly versatile materials that have garnered substantial attention in the domain of virus purification and chromatography processes designed for virus removal. These adsorbents, often derived from natural sources like agarose or cellulose, possess unique properties that make them suitable for virus removal. Notably, their preeminent attribute lies in their remarkable binding capacity for viruses, an attribute of paramount significance, facilitating the expeditious and efficient removal of viruses during the meticulous choreography of chromatographic procedures.
Table 1. The three main polysaccharides used as base materials for chromatography adsorbents. (Junter GA, Lebrun L. 2020)
| Polysaccharides |
Origins |
Agarose
Linear polysaccharide made up from alternating D-galactose and 3,6-anhydro-alpha-L-galactopyranose residues joined by α(1→3)- and β(1→4)-linkages |
Marine red algae (Rhodophyceae) |
Cellulose
β(1→4)-linked D-glucose residues (cellobiose units) |
Plants (flax, cotton…)
Bacterial fermentation («bacterial cellulose»)
(Gluconacetobacter xylinus) |
Dextran
Main chains consist of α(1→6)-linked D-glucose residues while side chains begin from α(1→3) linkages |
Bacterial fermentation (Leuconostoc mesenteroides, Streptococcus mutans) |
Several factors contribute to the effectiveness of polysaccharide adsorbents in virus purification:
Selectivity: Polysaccharide-based adsorbents can be engineered to exhibit high selectivity for specific viruses. This selectivity is crucial for ensuring that only the target virus is removed while preserving the integrity of the biopharmaceutical product.
Low leaching: Polysaccharide adsorbents are known for their minimal leaching of impurities into the final product, making them ideal for pharmaceutical applications where product purity is paramount.
Scalability: These adsorbents are available in various particle sizes and formats, making them suitable for both lab-scale research and large-scale manufacturing processes.
Particulate Resins
Particulate resins represent another class of adsorbents widely utilized in the domain of virus purification and chromatographic removal. These resins are characterized by their minute, spherical particles boasting an extensive surface area, which imparts a notable efficiency in virus binding. Particulate resins confer several distinct advantages in the context of virus removal processes:
High binding capacity: The large surface area of particulate resins allows for a high binding capacity, enabling the removal of a significant amount of virus particles in a single chromatographic run.
Rapid kinetics: Particulate resins provide fast kinetics, which is essential for minimizing process time and increasing overall productivity.
Regenerability: Many particulate resins are designed for multiple uses, making them cost-effective and environmentally friendly options for virus removal processes.
Versatility: Particulate resins are available in a variety of chemistries, allowing for customization to specific virus removal requirements.
Membrane Adsorbers
Membrane adsorbers represent a relatively recent yet highly effective approach to virus purification and chromatography. These adsorbers are composed of porous membranes functionalized with selective ligands or functional groups, enabling the specific capture of viruses. Membrane adsorbers offer several key advantages in virus removal processes:
High flow rates: Membrane adsorbers enable high flow rates, reducing process time and increasing throughput. This is especially important for large-scale manufacturing.
Scalability: These adsorbers are easily scalable and can be adapted to various chromatography system configurations.
Reduced buffer consumption: Membrane adsorbers require smaller volumes of buffer solution, resulting in cost savings and reduced environmental impact.
Enhanced virus removal: The selective ligands on membrane adsorbers can be tailored to target specific viruses, ensuring high removal efficiency.
Continuous processing: Membrane adsorbers are well-suited for continuous chromatography processes, which are becoming increasingly popular in the biopharmaceutical industry due to their efficiency and reduced operational costs.
Reference
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Junter GA, Lebrun L. Polysaccharide-based chromatographic adsorbents for virus purification and viral clearance. J Pharm Anal. 2020; 10(4):291-312.
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