Control of leached beta-glucan levels from depth filters by an improved depth filtration flush strategy. 2021

Melissa Holstein, and Dongyoun Jang, and Christine Urrea, and Lakshmi Sirisha Botta, and William Grimm, and Sanchayita Ghose, and Zheng Jian Li
Biologics Process Development, Global Product Development and Supply, Bristol-Myers Squibb Co., Devens, Massachusetts, USA.

Beta-glucans are polysaccharides of D-glucose monomers linked by (1-3) beta-glycosidic bonds, are found to have a potential immunogenicity risk in biotherapeutic products, and are labeled as process contaminants. A common source of beta-glucans is from the cellulose found in traditional depth filter media. Typically, beta-glucan impurities that leach into the product from the primary clarification depth filters can be removed by the subsequent bind-and-elute affinity chromatography capture step. Beta-glucans can also be removed by a bind-and-elute cation exchange chromatography step, which is useful for removing beta-glucans introduced by a post-Protein A depth filtration step. However, the increasing prevalence of flowthrough polishing chromatography poses a challenge for beta-glucan removal due to the lack of any bind-and-elute chromatography steps after the post-Protein A depth filter. In this work, a depth filter flush strategy was developed to control beta-glucan leaching into the product pool. Different loading conditions for the depth filtration and subsequent chromatography steps were evaluated to determine the robustness of the optimized flush strategy. Carry through runs demonstrated greater than two-fold reduction in beta-glucan levels using the optimized wash as compared to standard filter flush conditions.

UI MeSH Term Description Entries
D007074 Immunoglobulin G The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B. Gamma Globulin, 7S,IgG,IgG Antibody,Allerglobuline,IgG(T),IgG1,IgG2,IgG2A,IgG2B,IgG3,IgG4,Immunoglobulin GT,Polyglobin,7S Gamma Globulin,Antibody, IgG,GT, Immunoglobulin
D008567 Membranes, Artificial Artificially produced membranes, such as semipermeable membranes used in artificial kidney dialysis (RENAL DIALYSIS), monomolecular and bimolecular membranes used as models to simulate biological CELL MEMBRANES. These membranes are also used in the process of GUIDED TISSUE REGENERATION. Artificial Membranes,Artificial Membrane,Membrane, Artificial
D002846 Chromatography, Affinity A chromatographic technique that utilizes the ability of biological molecules, often ANTIBODIES, to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Chromatography, Bioaffinity,Immunochromatography,Affinity Chromatography,Bioaffinity Chromatography
D005374 Filtration A process of separating particulate matter from a fluid, such as air or a liquid, by passing the fluid carrier through a medium that will not pass the particulates. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Filtrations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D047071 beta-Glucans Glucose polymers consisting of a backbone of beta(1->3)-linked beta-D-glucopyranosyl units with beta(1->6) linked side chains of various lengths. They are a major component of the CELL WALL of organisms and of soluble DIETARY FIBER. beta-Glucan,beta Glucan,beta Glucans

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