Abstract：
In the current transition to intensified upstream processing, the risks of adopting traditional single-use systems for high-titer, long-duration perfusion cultures, have thus far not been considered. This case study uses the Failure Modes and Effects Analysis (FMEA) method to evaluate the risks associated with implementing upstream single-use technology. The simulated model process was used to compare the risk level of single-use technology for a traditional fed-batch cell culture with that for perfusion culture, under the same annual protein production conditions. To provide a reasonable source of potential risk for FMEA, all single-use upstream operations for both fed-batch and perfusion processes were investigated using an analytical method developed to quantify the impact of process parameters and operating conditions on single-use system specifications and to ensure objectivity. Many of the risks and their levels, were similar in long-duration perfusion cultures and fed-batch cultures. However, differences were observed for high-risk components such as daily sampling and installation. The result of this analysis indicates that the reasons for risk are different for fed-batch cultures and perfusion cultures such as larger bioreactors in fed-batch and longer runs in perfusion, respectively. This risk assessment method could identify additional control measures and be part of a holistic contamination control strategy and help visualize their effectiveness.
摘要：
在当前向强化上游加工过渡的过程中,采用传统的一次性使用系统进行高滴度的风险，长时间灌注培养，到目前为止还没有被考虑。本案例研究使用故障模式和影响分析（FMEA）方法来评估与实施上游一次性使用技术相关的风险。模拟模型过程用于比较传统补料分批细胞培养和灌注培养的一次性技术的风险水平。在相同的年度蛋白质生产条件下。为FMEA提供合理的潜在风险来源，使用一种分析方法对分批补料和灌注过程的所有一次性上游操作进行了调查,该分析方法旨在量化过程参数和操作条件对一次性使用系统规格的影响并确保客观性.许多风险及其水平，在长时间灌注培养和补料分批培养中相似。然而,观察到高风险组件的差异，例如每日采样和安装。该分析的结果表明，补料分批培养和灌注培养的风险原因不同，例如补料分批培养中的较大生物反应器和灌注中的较长运行时间，分别。这种风险评估方法可以确定其他控制措施，并成为整体污染控制策略的一部分，并有助于可视化其有效性。
