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Functional modification of protein therapeutics and its impact on production technologies
Journal of Bioscience and Bioengineering VOL. 108 No. S1, S21 – S28, 2009 www.elsevier.com/locate/jbiosc
Abstracts
Section II Biopharmaceuticals Production
BP-K1
BP-K2
Functional modification of protein therapeutics and its impact on production technologies
Developing new technologies for continuous manufacturing of recombinant proteins: When to innovate? What are the barriers? What are the challenges?
Toshiyuki Suzawa Konstantin Konstantinov, Peter McDonnell, and Blair Okita Kyowa Hakko Kirin Co., Ltd., Takasaki-shi, Gunma, Japan Genzyme Corporation, Framingham, MA, USA This presentation overviews advantage and current progress of functional modification of protein therapeutics and its impact on production technology in biopharmaceutical industry. Protein therapeutics, especially monoclonal antibodies, have made a rapid progress since late 1990s and more than 20 antibody products have been marketed so far. Thanks to the remarkable breakthrough in production technology at very large cell culture facilities, these new products requiring high therapeutic doses have been positioned in practical use. However, prohibitively high production cost can still be pushing medicinal expenses and be recognized as untenable aspects. To overcome this drawback, additional breakthrough will be essential for the future biopharmaceutical industry. One approach for reducing the cost of goods is to reinforce productivity using existing infrastructures. Since facility expansion and scale-up ration are apparently limiting factors, production titer in cell culture looks to be one of the major focus in the recent R&D activities. Another outstanding approach will be to improve biological function of the molecule to be developed. For example, POTELLIGENT(R) technology provides an opportunity to bring monoclonal antibody therapeutics with more than 100-fold higher antibody-dependent cellular cytotoxicity than the past conventional antibodies by eliminating fucose moiety of the N-type carbohydrates presented as a common structure of the molecule. As another example, modification of protein therapeutics using certain polymers like polyethylene glycols as well as conjugation of certain drugs with antibodies can bring significantly improved properties to the molecules. If such an improved function could be added onto the therapeutics, they may exert desired therapeutic efficacy even with quite smaller administration doses. Once such an improved technology becomes practically available, manufacturing capacity can be significantly reduced and, therefore, very large facilities might not necessarily be required. Thus, functional modification technology may provide some potential cornerstones impacting on manufacturing costs of biopharmaceuticals in the coming decades. doi:10.1016/j.jbiosc.2009.08.097
Genzyme has developed and implemented several large scale continuous processes for manufacturing of therapeutic proteins and synthetic molecules. While the corresponding technology platforms have evolved independently, there are multiple essential concepts and approaches that are compatible. We will review these similarities and will explore the synergistic opportunities to bridge knowledge in these two areas, including process design concepts, new technologies, and logistics. doi:10.1016/j.jbiosc.2009.08.098
BP-O1 Rapid response bioprocessing of influenza vaccines Nani Wibowo, Tania Rivera-Hernandez, Yuan-Yuan Fan, Cindy Chang, Yap Pang Chuan, Linda Lua, and Anton Middelberg University of Queensland, Brisbane, Queensland, Australia Influenza viruses continuously undergo variation (antigenic drift and antigenic shift) to evade the immune system of the host, which means the composition of the pandemic virus is not known in advance (1). The bottleneck to mass immunization increasingly lies in the area of product manufacture, and in particular the recovery and purification of product from an often complex mixture without causing loss of product efficacy. Current vaccine manufacturing technology, which begins by making an infectious virus in embryonated chicken eggs or cell culture, is unable to quickly deliver a mass vaccine to the population (2). It will take several months before enough vaccine is available even to protect personnel working in essential services. Our objective is to break the vaccine manufacturing bottleneck to enable full immunization of the population using existing biomanufacturing capability, within weeks of new strain identification, and without the requirement for high-level containment during manufacture.
Abstracts
Section II Biopharmaceuticals Production
BP-K1
BP-K2
Functional modification of protein therapeutics and its impact on production technologies
Developing new technologies for continuous manufacturing of recombinant proteins: When to innovate? What are the barriers? What are the challenges?
Toshiyuki Suzawa Konstantin Konstantinov, Peter McDonnell, and Blair Okita Kyowa Hakko Kirin Co., Ltd., Takasaki-shi, Gunma, Japan Genzyme Corporation, Framingham, MA, USA This presentation overviews advantage and current progress of functional modification of protein therapeutics and its impact on production technology in biopharmaceutical industry. Protein therapeutics, especially monoclonal antibodies, have made a rapid progress since late 1990s and more than 20 antibody products have been marketed so far. Thanks to the remarkable breakthrough in production technology at very large cell culture facilities, these new products requiring high therapeutic doses have been positioned in practical use. However, prohibitively high production cost can still be pushing medicinal expenses and be recognized as untenable aspects. To overcome this drawback, additional breakthrough will be essential for the future biopharmaceutical industry. One approach for reducing the cost of goods is to reinforce productivity using existing infrastructures. Since facility expansion and scale-up ration are apparently limiting factors, production titer in cell culture looks to be one of the major focus in the recent R&D activities. Another outstanding approach will be to improve biological function of the molecule to be developed. For example, POTELLIGENT(R) technology provides an opportunity to bring monoclonal antibody therapeutics with more than 100-fold higher antibody-dependent cellular cytotoxicity than the past conventional antibodies by eliminating fucose moiety of the N-type carbohydrates presented as a common structure of the molecule. As another example, modification of protein therapeutics using certain polymers like polyethylene glycols as well as conjugation of certain drugs with antibodies can bring significantly improved properties to the molecules. If such an improved function could be added onto the therapeutics, they may exert desired therapeutic efficacy even with quite smaller administration doses. Once such an improved technology becomes practically available, manufacturing capacity can be significantly reduced and, therefore, very large facilities might not necessarily be required. Thus, functional modification technology may provide some potential cornerstones impacting on manufacturing costs of biopharmaceuticals in the coming decades. doi:10.1016/j.jbiosc.2009.08.097
Genzyme has developed and implemented several large scale continuous processes for manufacturing of therapeutic proteins and synthetic molecules. While the corresponding technology platforms have evolved independently, there are multiple essential concepts and approaches that are compatible. We will review these similarities and will explore the synergistic opportunities to bridge knowledge in these two areas, including process design concepts, new technologies, and logistics. doi:10.1016/j.jbiosc.2009.08.098
BP-O1 Rapid response bioprocessing of influenza vaccines Nani Wibowo, Tania Rivera-Hernandez, Yuan-Yuan Fan, Cindy Chang, Yap Pang Chuan, Linda Lua, and Anton Middelberg University of Queensland, Brisbane, Queensland, Australia Influenza viruses continuously undergo variation (antigenic drift and antigenic shift) to evade the immune system of the host, which means the composition of the pandemic virus is not known in advance (1). The bottleneck to mass immunization increasingly lies in the area of product manufacture, and in particular the recovery and purification of product from an often complex mixture without causing loss of product efficacy. Current vaccine manufacturing technology, which begins by making an infectious virus in embryonated chicken eggs or cell culture, is unable to quickly deliver a mass vaccine to the population (2). It will take several months before enough vaccine is available even to protect personnel working in essential services. Our objective is to break the vaccine manufacturing bottleneck to enable full immunization of the population using existing biomanufacturing capability, within weeks of new strain identification, and without the requirement for high-level containment during manufacture.