Gottschalk Uwe
Sartorius-Stedim Biotech, August-Spindler-Strasse 11, 37079 Goettingen, Germany.
Biotechnol Prog. 2008 May-Jun;24(3):496-503. doi: 10.1021/bp070452g. Epub 2008 Apr 29.
Improvements in upstream production have boosted productivity in the biomanufacturing industry, but this is leading to bottlenecks in downstream processing as current technology platforms reach their limits of throughput and scalability. Although chromatography remains an indispensible component of downstream processing due to its simplicity and high resolving power (The Good), there is virtually no economy of scale effect so more product translates almost linearly into greater production costs. Bind-and-elute processes (such as the initial capture step in antibody manufacturing) are volume-driven and therefore have knock-on effects that impact on the entire production facility since the space required for preparation, storage, and cleaning steps has to be similarly adapted (The Bad). During long-term operations with multiple cycles, thorough cleaning is necessary to prevent progressive fouling and microbial contamination (The Ugly). Innovative solutions are required, which may include revisiting simpler and less expensive separation technologies, the use of disposable modules, and the integration of improved processes that are scalable to cope with increased demands. Among the alternatives that have been put forward, membrane adsorbers are beginning to make a real impact on the industry, particularly for flow-through applications such as polishing and viral clearance.
上游生产的改进提高了生物制造业的生产力，但由于当前技术平台达到了其通量和可扩展性的极限，这正导致下游加工出现瓶颈。尽管色谱法因其简单性和高分辨率仍是下游加工中不可或缺的组成部分（优点），但几乎不存在规模经济效应，因此更多的产品几乎会直接转化为更高的生产成本。结合洗脱过程（如抗体生产中的初始捕获步骤）是受体积驱动的，因此会产生连锁反应，影响整个生产设施，因为制备、储存和清洗步骤所需的空间也必须相应调整（缺点）。在多循环的长期操作过程中，必须进行彻底清洗以防止渐进性污染和微生物污染（麻烦之处）。需要创新的解决方案，这可能包括重新审视更简单、成本更低的分离技术，使用一次性模块，以及整合可扩展以应对不断增加的需求的改进工艺。在已提出的替代方案中，膜吸附剂开始对该行业产生实际影响，特别是对于诸如精制和病毒清除等流通应用。
