Nelson K L, Geyer S
Stearns Catalytic Division, United Engineers & Constructors, Philadelphia, Pennsylvania.
Bioprocess Technol. 1991;13:112-43.
Good Manufacturing Practice for pharmaceuticals requires that the manufacturing processes be controlled and reproducible. The biological nature of cell culture-based processes lends them an inherently higher variability than is generally found for processes involving production of defined chemical entities. As one regulatory body has pointed out, this places a greater emphasis on in-process controls and adherence to GMPs in the manufacture of cell culture products. Design of bioreactors and associated process control systems is a key element in the successful implementation of a commercial-scale cell culture manufacturing process capable of meeting such high standards. It should be noted that reactor and control system designs for animal cell culture are still very much in a state of evolution from the modified bacterial fermentation systems that currently predominate, and it is difficult to predict how design strategies may change in the coming years. Having said this, however, it should be clear from the information presented here that satisfactory processes can be devised today using proven equipment configurations such as the stirred-tank reactor.
药品生产质量管理规范要求生产过程得到控制且具有可重复性。基于细胞培养的生产过程的生物学特性使其固有变异性高于一般涉及特定化学实体生产的过程。正如一个监管机构所指出的，这使得在细胞培养产品生产中更加强调过程控制和对药品生产质量管理规范的遵守。生物反应器及相关过程控制系统的设计是成功实施能够达到如此高标准的商业规模细胞培养生产过程的关键要素。应当注意的是，动物细胞培养的反应器和控制系统设计仍在很大程度上从目前占主导地位的改良细菌发酵系统演变而来，并且很难预测未来几年设计策略会如何变化。然而，尽管如此，从这里给出的信息中应该清楚的是，如今使用如搅拌罐式反应器等经过验证的设备配置可以设计出令人满意的生产过程。
