Institute for Separation and Process Technology, Clausthal University of Technology, Clausthal-Zellerfeld, Germany.
Adv Biochem Eng Biotechnol. 2021;176:181-262. doi: 10.1007/10_2020_146.
In recent years process modelling has become an established method which generates digital twins of manufacturing plant operation with the aid of numerically solved process models. This article discusses the benefits of establishing process modelling, in-house or by cooperation, in order to support the workflow from process development, piloting and engineering up to manufacturing. The examples are chosen from the variety of botanicals and biologics manufacturing thus proving the broad applicability from variable feedstock of natural plant extracts of secondary metabolites to fermentation of complex molecules like mAbs, fragments, proteins and peptides.Consistent models and methods to simulate whole processes are available. To determine the physical properties used as model parameters, efficient laboratory-scale experiments are implemented. These parameters are case specific since there is no database for complex molecules of biologics and botanicals in pharmaceutical industry, yet.Moreover, Quality-by-Design approaches, demanded by regulatory authorities, are integrated within those predictive modelling procedures. The models could be proven to be valid and predictive under regulatory aspects. Process modelling does earn its money from the first day of application. Process modelling is a key-enabling tool towards cost-efficient digitalization in chemical-pharmaceutical industries.
近年来，过程建模已经成为一种成熟的方法，借助数值求解的过程模型，为制造工厂的运营生成数字孪生体。本文讨论了建立过程建模（内部建立或合作建立）的好处，以支持从工艺开发、中试到制造的工作流程。这些示例来自各种植物药和生物制药制造，从而证明了从天然植物提取物的二次代谢产物的可变原料到复杂分子（如单抗、片段、蛋白质和肽）的发酵的广泛适用性。可用于模拟整个过程的一致模型和方法。为了确定用作模型参数的物理特性，实施了高效的实验室规模实验。这些参数是特定于案例的，因为在制药行业中还没有用于生物制药和植物药的复杂分子的数据库。此外，监管机构要求的质量源于设计方法被整合到这些预测建模过程中。这些模型可以在监管方面被证明是有效的和可预测的。过程建模从应用的第一天就开始盈利。过程建模是化学制药行业实现成本效益数字化的关键使能工具。
