Purpose

There is a continuous search for efficient optimization methods in the production of biopharmaceuticals, with a special focus on reducing production time and costs. Pharmaceutical production is currently dominated by batch production processes that have a relatively long downtime for cleaning and reconfiguration of the plant equipment when the product or its format size is changed. The geometry and design of the equipment can strongly affect process performance. This work presents an approach for generating and assessing design alternatives for process equipment used in the sterile filling of biopharmaceutical drug products.

Methods

A case study is presented based on background information provided by Hoffmann-La Roche for a surge tank used in the filling of liquid vials. Three criteria—namely equipment cleanability, production efficiency, and flexibility—are used to evaluate the proposed shape alternatives for the surge tank. Computational fluid dynamics (CFD) was applied to investigate the flow behavior of cleaning water inside the tank.

Results

A trade-off in the results was observed between the different evaluation criteria for the investigated basic shapes. However, it was found that a different part of the tank controls the results obtained for each criterion. An alternative tank design is presented that combines the optimal features to achieve the best possible performance for all assessment criteria.

Conclusion

The transfer and application of the established CFD technique to the field of sterile manufacturing of biopharmaceuticals were demonstrated and facilitated by the introduction of appropriate model simplifications. Valuable insights on equipment cleanability and on the measures required to achieve cleanliness were obtained, which proves the importance of the application of such techniques. Redesigning equipment and applying geometrical changes were shown to be effective measures for process performance optimization.

中文翻译：

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生物制药无菌生产中多标准设备的重新设计方法

目的

在生物制药生产中一直在寻找有效的优化方法，特别是在减少生产时间和成本上。药品生产目前主要由批量生产过程控制，当产品或其格式尺寸发生更改时，该过程的停机时间相对较长，用于清洁和重新配置工厂设备。设备的几何形状和设计会严重影响过程性能。这项工作提出了一种方法，用于生成和评估用于无菌填充生物制药产品的工艺设备的设计替代方案。

方法

基于Hoffmann-La Roche提供的用于填充液体小瓶的调压罐的背景信息，进行了案例研究。使用三个标准（即设备的清洁性，生产效率和灵活性）来评估调压罐的备选形状。计算流体动力学（CFD）用于研究水箱内部清洁水的流动行为。

结果

对于所研究的基本形状，在不同的评估标准之间观察到结果之间的权衡。但是，发现储罐的不同部分控制着每个标准的结果。提出了一种替代性储罐设计，该储罐设计结合了最佳功能，可针对所有评估标准实现最佳性能。

结论

通过引入适当的模型简化，证明并促进了已建立的CFD技术在生物制药无菌制造领域的转移和应用。获得了关于设备可清洁性以及实现清洁所需的措施的宝贵见解，这证明了应用此类技术的重要性。重新设计设备和应用几何变化被证明是优化过程性能的有效措施。