The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, United Kingdom.
J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Jun 15;899:116-26. doi: 10.1016/j.jchromb.2012.05.010. Epub 2012 May 14.
An integrated experimental and modeling approach for the design of high productivity protein A chromatography is presented to maximize productivity in bioproduct manufacture. The approach consists of four steps: (1) small-scale experimentation, (2) model parameter estimation, (3) productivity optimization and (4) model validation with process verification. The integrated use of process experimentation and modeling enables fewer experiments to be performed, and thus minimizes the time and materials required in order to gain process understanding, which is of key importance during process development. The application of the approach is demonstrated for the capture of antibody by a novel silica-based high performance protein A adsorbent named AbSolute. In the example, a series of pulse injections and breakthrough experiments were performed to develop a lumped parameter model, which was then used to find the best design that optimizes the productivity of a batch protein A chromatographic process for human IgG capture. An optimum productivity of 2.9 kg L⁻¹ day⁻¹ for a column of 5mm diameter and 8.5 cm length was predicted, and subsequently verified experimentally, completing the whole process design approach in only 75 person-hours (or approximately 2 weeks).
提出了一种集成的实验和建模方法，用于设计高生产力的蛋白 A 色谱，以在生物制品制造中最大限度地提高生产力。该方法包括四个步骤：（1）小规模实验，（2）模型参数估计，（3）生产力优化，（4）通过过程验证进行模型验证。工艺实验和建模的综合使用可以减少实验次数，从而最大限度地减少获得工艺理解所需的时间和材料，这在工艺开发过程中至关重要。该方法的应用通过一种新型的基于硅胶的高性能蛋白 A 吸附剂 AbSolute 用于抗体的捕获来证明。在该示例中，进行了一系列脉冲注射和突破实验，以开发出一个集总参数模型，然后使用该模型找到最佳设计，以优化用于人 IgG 捕获的批处理蛋白 A 色谱过程的生产力。预测到 5mm 直径和 8.5cm 长度的柱的最佳生产力为 2.9kg L ⁻¹ 天 ⁻¹ ，随后通过实验进行了验证，仅用 75 个人时（或大约 2 周）就完成了整个过程设计方法。
