Global Process Development Analytics, Bristol-Myers Squibb Company, Devens, Massachusetts, USA.
Biologics Analytical Development & Attribute Sciences, Bristol-Myers Squibb Company, Devens, Massachusetts, USA.
Biotechnol Prog. 2021 Jul;37(4):e3177. doi: 10.1002/btpr.3177. Epub 2021 May 31.
Analytical testing of product quality attributes and process parameters during the biologics development (Process analytics) has been challenging due to the rapid growth of biomolecules with complex modalities to support unmet therapeutic needs. Thus, the expansion of the process analytics tool box for rapid analytics with the deployment of cutting-edge technologies and cyber-physical systems is a necessity. We introduce the term, Process Analytics 4.0; which entails not only technology aspects such as process analytical technology (PAT), assay automation, and high-throughput analytics, but also cyber-physical systems that enable data management, visualization, augmented reality, and internet of things (IoT) infrastructure for real time analytics in process development environment. This review is exclusively focused on dissecting high-level features of PAT, automation, and data management with some insights into the business aspects of implementing during process analytical testing in biologics process development. Significant technological and business advantages can be gained with the implementation of digitalization, automation, and real time testing. A systematic development and employment of PAT in process development workflows enable real time analytics for better process understanding, agility, and sustainability. Robotics and liquid handling workstations allow rapid assay and sample preparation automation to facilitate high-throughput testing of attributes and molecular properties which are otherwise challenging to monitor with PAT tools due to technological and business constraints. Cyber-physical systems for data management, visualization, and repository must be established as part of Process Analytics 4.0 framework. Furthermore, we review some of the challenges in implementing these technologies based on our expertise in process analytics for biopharmaceutical drug substance development.
由于生物分子的快速增长具有复杂的模式，需要支持未满足的治疗需求，因此在生物制品开发过程中（过程分析）对产品质量属性和工艺参数进行分析测试一直具有挑战性。因此，必须扩展过程分析工具包，以便使用先进技术和网络物理系统进行快速分析。我们引入了“过程分析 4.0”这一术语；这不仅需要技术方面的知识，例如过程分析技术（PAT）、分析自动化和高通量分析，还需要网络物理系统来实现数据管理、可视化、增强现实和物联网 (IoT) 基础设施，以便在过程开发环境中进行实时分析。本文专门侧重于剖析 PAT、自动化和数据管理的高级特性，并深入探讨在生物制品过程开发中进行过程分析测试时实施这些特性的业务方面。通过实施数字化、自动化和实时测试，可以获得显著的技术和业务优势。系统地开发和采用 PAT 可以在过程开发工作流程中实现实时分析，从而更好地理解、灵活应对和保持可持续性。机器人和液体处理工作站允许快速进行分析和样品制备自动化，以促进高通量测试属性和分子特性，由于技术和业务方面的限制，这些特性很难通过 PAT 工具进行监测。数据管理、可视化和存储库的网络物理系统必须作为过程分析 4.0 框架的一部分建立。此外，我们根据在生物制药药物开发过程分析方面的专业知识，审查了实施这些技术所面临的一些挑战。
