Merck & Co., Inc., Kenilworth, New Jersey, USA.
Bristol-Myers Squibb, Devens, Massachusetts, USA.
Biotechnol Bioeng. 2022 Feb;119(2):423-434. doi: 10.1002/bit.27990. Epub 2021 Dec 13.
The application of process analytical technology (PAT) for biotherapeutic development and manufacturing has been employed owing to technological, economic, and regulatory advantages across the industry. Typically, chromatographic, spectroscopic, and/or mass spectrometric sensors are integrated into upstream and downstream unit operations in in-line, on-line, or at-line fashion to enable real-time monitoring and control of the process. Despite the widespread utility of PAT technologies at various unit operations of the bioprocess, a holistic business value assessment of PAT has not been well addressed in biologics. Thus, in this study, we evaluated PAT technologies based on predefined criteria for their technological attributes such as enablement of better process understanding, control, and high-throughput capabilities; as well as for business attributes such as simplicity of implementation, lead time, and cost reduction. The study involved an industry-wide survey, where input from subject matter industry experts on various PAT tools were collected, assessed, and ranked. The survey results demonstrated on-line liquid Chromatography (LC), in-line Raman, and gas analysis techniques are of high business value especially at the production bioreactor unit operation of upstream processing. In-line variable path-length UV/VIS measurements (VPE), on-line LC, multiangle light scattering (MALS), and automated sampling are of high business value in Protein A purification and polishing steps of the downstream process. We also provide insights, based on our experience in clinical and commercial manufacturing of biologics, into the development and implementation of some of the PAT tools. The results presented in this study are intended to be helpful for the current practitioners of PAT as well as those new to the field to gauge, prioritize and steer their projects for success.
由于在整个行业中具有技术、经济和监管优势，过程分析技术（PAT）已被应用于生物治疗药物的开发和制造。通常，色谱、光谱和/或质谱传感器以在线、在线或离线的方式集成到上游和下游单元操作中，以实现对过程的实时监测和控制。尽管 PAT 技术在生物工艺的各种单元操作中得到了广泛应用，但生物制品中尚未很好地解决 PAT 的整体业务价值评估问题。因此，在本研究中，我们根据技术属性（例如更好地理解、控制和高通量能力的实现）和业务属性（例如实施的简单性、前置时间和成本降低），基于预定义的标准来评估 PAT 技术。该研究涉及一项行业范围的调查，其中收集、评估和排名了来自各个 PAT 工具的主题行业专家的意见。调查结果表明，在线液相色谱（LC）、在线拉曼和气体分析技术具有很高的业务价值，特别是在生物上游处理的生产生物反应器单元操作中。在线可变光路长度紫外/可见（VPE）测量、在线 LC、多角度光散射（MALS）和自动采样在下游工艺的蛋白 A 纯化和抛光步骤中具有很高的业务价值。我们还根据我们在生物制品临床和商业生产方面的经验，深入了解了一些 PAT 工具的开发和实施。本研究的结果旨在为当前的 PAT 从业者以及该领域的新手提供帮助，帮助他们评估、确定优先级并指导项目取得成功。
