Continuous improvements of cell‐free synthesis (CFS) systems have generated interest in adopting the technology for the manufacture of biologics. This paper provides an evaluation of the manufacturing cost‐effectiveness of CFS for the commercial production of antibody‐drug conjugates (ADCs). The evaluation was performed using an advanced techno‐economic engine (TEE) built in Python. The TEE is programmed in an object‐oriented environment capable of simulating a plethora of process flowsheets and predicting size and cost metrics for the process and the facility. A case study was formulated to compare the economics of whole bioprocesses based on either a CFS system or a mammalian cell system (CHO) for the manufacture of an ADC at a range of product demands. The analysis demonstrated the potential of CFS for the commercial manufacture of biologics and identified key cost drivers related to the system. The CFS system showed an approximately 80% increase in the cost of goods compared to CHO with a significant cost attributed to the in‐house manufacture of the bacterial cell extract, necessary for the CFS reaction step in the process. A sensitivity and target analysis highlighted the need for further process improvements especially in the titer for the CFS process to become more competitive against well‐established systems.

中文翻译：

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商业生产抗体药物偶联物的无细胞合成的过程经济学评估

无细胞合成（CFS）系统的不断改进引起了人们对该技术用于生物制剂生产的兴趣。本文评估了CFS在抗体药物偶联物（ADC）的商业生产中的制造成本效益。评估是使用Python内置的高级技术经济引擎（TEE）进行的。在面向对象的环境中对TEE进行编程，该环境能够模拟大量过程流程图，并预测过程和设施的规模和成本指标。制定了一个案例研究，以比较基于CFS系统或哺乳动物细胞系统（CHO）的整个生物过程在一系列产品需求下制造ADC的经济性。分析显示了CFS在生物制剂商业生产中的潜力，并确定了与该系统相关的关键成本驱动因素。与CHO相比，CFS系统的商品成本增加了约80％，其中很大的成本归因于细菌细胞提取物的内部制造，这是该过程中CFS反应步骤所必需的。敏感性和目标分析强调了需要进一步改进流程，尤其是在CFS流程的效价方面，以使其与完善的系统相比更具竞争力。