Dept. of Chemical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, India.
Biotechnol Prog. 2010 Mar-Apr;26(2):448-57. doi: 10.1002/btpr.320.
Process Analytical Technology (PAT) has been gaining a lot of momentum in the biopharmaceutical community because of the potential for continuous real time quality assurance resulting in improved operational control and compliance. In previous publications, we have demonstrated feasibility of applications involving use of high performance liquid chromatography (HPLC) and ultra performance liquid chromatography (UPLC) for real-time pooling of process chromatography column. In this article we follow a similar approach to perform lab studies and create a model for a chromatography step of a different modality (hydrophobic interaction chromatography). It is seen that the predictions of the model compare well to actual experimental data, demonstrating the usefulness of the approach across the different modes of chromatography. Also, use of online HPLC when the step is scaled up to pilot scale (a 2294 fold scale-up from a 3.4 mL column in the lab to a 7.8 L column in the pilot plant) and eventually to manufacturing scale (a 45930 fold scale-up from a 3.4 mL column in the lab to a 158 L column in the manufacturing plant) is examined. Overall, the results confirm that for the application under consideration, online-HPLC offers a feasible approach for analysis that can facilitate real-time decisions for column pooling based on product quality attributes. The observations demonstrate that the proposed analytical scheme allows us to meet two of the key goals that have been outlined for PAT, i.e., "variability is managed by the process" and "product quality attributes can be accurately and reliably predicted over the design space established for materials used, process parameters, manufacturing, environmental, and other conditions". The application presented here can be extended to other modes of process chromatography and/or HPLC analysis.
过程分析技术（PAT）在生物制药界越来越受到关注，因为它有可能实现连续实时的质量保证，从而改善操作控制和合规性。在之前的出版物中，我们已经证明了涉及使用高效液相色谱（HPLC）和超高效液相色谱（UPLC）实时汇集过程色谱柱的应用的可行性。在本文中，我们采用类似的方法进行实验室研究，并为不同模式（疏水相互作用色谱）的色谱步骤创建模型。结果表明，模型的预测与实际实验数据吻合较好，证明了该方法在不同模式的色谱中的有用性。此外，当该步骤放大到中试规模（从实验室的 3.4 mL 柱放大到中试工厂的 7.8 L 柱，放大 2294 倍），最终放大到生产规模（从实验室的 3.4 mL 柱放大到生产工厂的 158 L 柱，放大 45930 倍）时，考察了在线 HPLC 的使用。总的来说，结果证实，对于所考虑的应用，在线 HPLC 为分析提供了一种可行的方法，可以根据产品质量属性为柱汇集做出实时决策。观察结果表明，所提出的分析方案使我们能够满足 PAT 提出的两个关键目标，即“通过过程管理变异性”和“可以在为所用材料、工艺参数、制造、环境和其他条件建立的设计空间中准确可靠地预测产品质量属性”。本文介绍的应用可以扩展到其他过程色谱和/或 HPLC 分析模式。
