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Extrusion/Spheronization as a Granulation Technique
Published in Dilip M. Parikh, Handbook of Pharmaceutical Granulation Technology, 2021
Regardless of the mixer used, one must remember that the downstream process steps of extrusion and spheronization are very dependent on the level of granulating fluid contained in the granulation and the quality of its dispersion. Over or under-wet granulations can cause an abundance of coarse or fine particles, respectively, while uneven wetting can cause a high degree of variation in particle size within the batch over the processing period. High-energy mixers such as high-shear mixers and high-shear twin screw mixer/extruders can cause a significant rise in temperature within the wet mass. It may be necessary to use a jacket to guard against heat build-up. High temperatures can result in a greater than tolerable level of evaporation or an increase in the solubility of some of the solids as demonstrated by L. Baert et al. [49,51]. A reduction in a fluid will reduce the plasticity of the granulation. This will likely cause a finer, more porous, less dense, less uniform, and less spherical granulation to be produced. The objective of downstream processing will determine if some of these effects are desirable or not. If the effects of less fluid are desirable, it is better to add less fluid, control the environmental conditions, and understand the effects of process variables, such as speed and time. If the effects of less fluid are undesirable, greater fluid and effective use of process variables to control the process are again necessary.
Potentials and Challenges in the Production of Microalgal Pigments with Reference to Carotenoids, Chlorophylls, and Phycobiliproteins
Published in Gokare A. Ravishankar, Ranga Rao Ambati, Handbook of Algal Technologies and Phytochemicals, 2019
Delia B. Rodriguez-Amaya, Iriani R. Maldonade
Downstream processing, especially cell harvesting and disruption, is challenging. Centrifugation is fast, efficient, suitable for most strains, and most widely applied for harvesting microalgae (Gong and Bassi, 2016). However, it demands high capital cost and continuous energy investment. Filtration is time and energy consuming for small size microalgae. Gravity sedimentation is inexpensive, but requires a long time for small, uniformly suspended cells when no additional flocculants are present. Chemical harvesting methods require lower capital investment and consume much less energy but are not as efficient as mechanical methods. Flocculation has received much attention because of the possibility of treating large-scale microalgal suspensions at a lower cost.
Use of Enzymes in the Downstream Processing of Biopharmaceuticals
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
The manufacturing of biopharmaceuticals encompasses a string of activities that are designed with the goal of producing a certain mass or biological activity of a target product with specific quality attributes. These activities can be grouped into two stages: the upstream processing, which comprises the generation of cell lines/strains, the establishment of cell banks, inoculum preparation and cell cultivation, and the downstream processing, which includes all the unit operations required to purify the product up to a point where pre-defined, end-product specifications are met (Heinzle et al., 2006; Jungbauer, 2013).
Untargeted proteomics reveals upregulation of stress response pathways during CHO-based monoclonal antibody manufacturing process leading to disulfide bond reduction
Published in mAbs, 2021
Seo-Young Park, Susan Egan, Anthony J. Cura, Kathryn L. Aron, Xuankuo Xu, Mengyuan Zheng, Michael Borys, Sanchayita Ghose, Zhengjian Li, Kyongbum Lee
Reduction of mAb interchain disulfide bonds has been observed at various stages during downstream processing following bioreactor harvest.6 Studies aimed at identifying the factors that contribute to this phenomenon have largely focused on the role of downstream processing conditions. For example, Trexler-Schmidt et al.7 attributed antibody disulfide reduction to intracellular reducing enzymes (primarily thioredoxin reductase/thioredoxin) that are released when cell lysis occurs due to harsh centrifugation conditions during harvest. Accordingly, efforts to minimize the formation of low molecular weight (LMW) disulfide reduction products have focused on modifying harvest-related processing steps. One proposed solution is to maintain a highly oxidative environment in the harvested cell culture fluid (HCCF) through air sparging for the purpose of shifting the equilibrium of reversible redox reactions toward oxidation.8 Another strategy is to minimize the activity of host cell-derived reducing enzymes by reducing storage temperature,6,9,10 adding chemical inhibitors (e.g., cystine, copper sulfate, ethylenediamine tetraacetic acid) or removing cofactors for the enzymes (e.g., metal ions).7
Investigation of a monoclonal antibody against enterotoxigenic Escherichia coli, expressed as secretory IgA1 and IgA2 in plants
Published in Gut Microbes, 2021
Audrey Y-H Teh, Lisa Cavacini, Yue Hu, Ozan S. Kumru, Jian Xiong, David T. Bolick, Sangeeta B. Joshi, Clemens Grünwald-Gruber, Friedrich Altmann, Mark Klempner, Richard L. Guerrant, David B. Volkin, Yang Wang, Julian K-C. Ma
This study indicates that protective anti-ETEC SIgA1 and SIgA2 antibodies can both be produced by N. benthamiana, and whilst further work is needed to consider best antigenic targets, the possibility of combining mAbs, to optimize alpha chain constant region sequences, maximize yields and establish more efficient extraction and purification processes, this would be a requirement for any expression system. A long-term aspiration, requiring more regulatory development, would be to express anti-ETEC secretory antibodies in edible plants, allowing direct administration by the oral route, as has been demonstrated by vaccine delivery using corn and potatoes for diarrheal and other diseases.46,47 This would simplify extraction and downstream processing, steps that are generally regarded as the major contributors to cost of goods.48,49
Optimization of a calcium-dependent Protein A-derived domain for mild antibody purification
Published in mAbs, 2019
Julia Scheffel, Sara Kanje, Jesper Borin, Sophia Hober
As the market for biotherapeutics expands and advances in upstream processing lead to accelerating cell culture titers, the pressure on downstream processing to develop more efficient processes is increasing. Since Protein A capture commonly is the initial purification step and a vital part of the downstream mAb process, it risks becoming a bottleneck for the whole manufacturing process. Thus, it is of great importance to increase the binding capacity of Protein A resins. Currently, various new Protein A resins offering higher dynamic binding capacities (DBCs) and improved process productivity are being launched to handle the high feed concentrations and large throughput. Many of these commercially available resins are made up from several repeated binding units, which in many cases have been shown to significantly increase the DBC of the ligand.20