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Manufacturing Economics of Plant-Made Biologics: Case Studies in Therapeutic and Industrial Enzymes

机译:植物生物制品的制造经济学:治疗和工业酶的案例研究

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摘要

Production of recombinant biologics in plants has received considerable attention as an alternative platform to traditional microbial and animal cell culture. Industrially relevant features of plant systems include proper eukaryotic protein processing, inherent safety due to lack of adventitious agents, more facile scalability, faster production (transient systems), and potentially lower costs. Lower manufacturing cost has been widely claimed as an intuitive feature of the platform by the plant-made biologics community, even though cost information resides within a few private companies and studies accurately documenting such an advantage have been lacking. We present two technoeconomic case studies representing plant-made enzymes for diverse applications: human butyrylcholinesterase produced indoors for use as a medical countermeasure and cellulases produced in the field for the conversion of cellulosic biomass into ethanol as a fuel extender. Production economics were modeled based on results reported with the latest-generation expression technologies on Nicotiana host plants. We evaluated process unit operations and calculated bulk active and per-dose or per-unit costs using SuperPro Designer modeling software. Our analyses indicate that substantial cost advantages over alternative platforms can be achieved with plant systems, but these advantages are molecule/product-specific and depend on the relative cost-efficiencies of alternative sources of the same product.
机译:作为传统微生物和动物细胞培养的替代平台,植物中重组生物制剂的生产已引起广泛关注。植物系统在工业上的相关特征包括正确的真核蛋白质加工,由于缺乏外来剂而产生的固有安全性,更易扩展的能力,更快的生产(瞬态系统)以及可能更低的成本。尽管成本信息存在于少数私人公司中,并且缺乏准确记录这种优势的研究,但制造人造生物界已普遍认为,较低的制造成本是该平台的直观功能。我们提供了两种代表各种用途的植物酶的技术经济案例研究:在室内生产的人丁酰胆碱酯酶,作为医学对策;在现场生产的纤维素酶,用于将纤维素生物质转化为乙醇作为燃料增量剂。生产经济学是根据烟草宿主植物上最新一代表达技术报告的结果进行建模的。我们使用SuperPro Designer建模软件评估了工艺单元的运行情况,并计算了总的有效量,每剂量或每单位成本。我们的分析表明,使用工厂系统可以在替代平台上实现实质性的成本优势,但是这些优势是分子/产品特定的,并且取决于同一产品替代来源的相对成本效率。

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