The move to integrated continuous bioprocessing (ICB), while providing a means for process intensification, can put added strain on process analytics when conventional methods are used. For instance, traditional microbial methods provide minimal value to ICB processes given that the time required for data to become available is much longer than a typical full cycle of the manufacturing process. Although rapid microbial detection has been in discussion for over 30 years, it is still not routinely deployed in commercial biopharmaceutical manufacturing. One contributing factor is the ability to integrate this technology into a process control strategy and existing quality systems. An understanding of the capability of microbial detection technology available today can be leveraged to implement a control strategy for bioburden monitoring in real time for process intermediates. One key tenet of this proposed control strategy is the use of a “two‐tiered approach” wherein a fast (but possibly less sensitive) test is used to monitor the process and trigger further action for a second, longer duration test which is used to confirm and quantify the presence of bioburden and identify the organism. This approach, presented here alongside several case studies for microbial monitoring, can have broader application for other process analytical technologies where fit for purpose methods could be employed to establish process control alongside real time continuous processes.

中文翻译：

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将快速生物负载测试集成到生产质量管理系统和过程控制中

转向集成连续生物处理（ICB）虽然提供了一种过程强化的手段，但在使用传统方法时可能会给过程分析带来额外的压力。例如，传统的微生物方法对 ICB 流程的价值微乎其微，因为数据可用所需的时间比制造流程的典型完整周期长得多。尽管快速微生物检测已经被讨论了 30 多年，但它仍然没有在商业生物制药生产中常规部署。一个促成因素是将这项技术集成到过程控制策略和现有质量体系中的能力。了解当今可用的微生物检测技术的能力可用于实施实时过程中间体生物负载监测的控制策略。该提议的控制策略的一个关键原则是使用“双层方法”，其中使用快速（但可能不太敏感）测试来监控过程并触发第二次持续时间较长的测试的进一步操作，该测试用于确认和量化生物负载的存在并识别生物体。这里介绍的这种方法与微生物监测的几个案例研究一起，可以在其他过程分析技术中具有更广泛的应用，在这些技术中，可以采用适合目的的方法来建立过程控制以及实时连续过程。