Hammerschmidt Nikolaus, Tscheliessnig Anne, Sommer Ralf, Helk Bernhard, Jungbauer Alois
Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, Vienna, Austria; Austria Centre for Industrial Biotechnology, Vienna, Austria.
Biotechnol J. 2014 Jun;9(6):766-75. doi: 10.1002/biot.201300480. Epub 2014 Apr 4.
Standard industry processes for recombinant antibody production employ protein A affinity chromatography in combination with other chromatography steps and ultra-/diafiltration. This study compares a generic antibody production process with a recently developed purification process based on a series of selective precipitation steps. The new process makes two of the usual three chromatographic steps obsolete and can be performed in a continuous fashion. Cost of Goods (CoGs) analyses were done for: (i) a generic chromatography-based antibody standard purification; (ii) the continuous precipitation-based purification process coupled to a continuous perfusion production system; and (iii) a hybrid process, coupling the continuous purification process to an upstream batch process. The results of this economic analysis show that the precipitation-based process offers cost reductions at all stages of the life cycle of a therapeutic antibody, (i.e. clinical phase I, II and III, as well as full commercial production). The savings in clinical phase production are largely attributed to the fact that expensive chromatographic resins are omitted. These economic analyses will help to determine the strategies that are best suited for small-scale production in parallel fashion, which is of importance for antibody production in non-privileged countries and for personalized medicine.
重组抗体生产的标准行业流程采用蛋白A亲和色谱法，并结合其他色谱步骤以及超滤/渗滤。本研究将一种通用的抗体生产工艺与最近开发的基于一系列选择性沉淀步骤的纯化工艺进行了比较。新工艺使通常的三个色谱步骤中的两个过时，并且可以连续进行。对以下方面进行了商品成本（CoGs）分析：（i）基于通用色谱的抗体标准纯化；（ii）与连续灌注生产系统相结合的基于连续沉淀的纯化工艺；（iii）一种混合工艺，即将连续纯化工艺与上游分批工艺相结合。该经济分析结果表明，基于沉淀的工艺在治疗性抗体生命周期的所有阶段（即临床I期、II期和III期以及全面商业化生产）都能降低成本。临床阶段生产中的成本节省主要归因于省去了昂贵的色谱树脂。这些经济分析将有助于确定最适合以并行方式进行小规模生产的策略，这对于非特权国家的抗体生产和个性化医疗具有重要意义。
