The production of commercially valuable biotherapeutic molecules in mammalian systems has expanded significantly in the last thirty years, but growing economic pressures within the industry are driving efforts to reduce costs and enhance process yields. At the upstream stage, two complementary approaches have evolved to increase productivity and maintain consistent product quality, that is either by altering the cell directly or by manipulating its environment. This review focuses on novel approaches to impact productivity and product quality by manipulating the environment through: (a) altering media composition; (b) modulating operating conditions such as pH and temperature; or (c) intensifying process operations by switching from fed-batch to continuous processes.

在过去的三十年中，哺乳动物系统中具有商业价值的生物治疗分子的生产已大大扩展，但是该行业内日益增长的经济压力正在推动降低成本和提高工艺产量的努力。在上游阶段，已经开发了两种互补的方法来提高生产率并保持一致的产品质量，即通过直接更改单元格或通过操纵其环境来实现。这篇综述着重于通过以下方式操纵环境来影响生产率和产品质量的新颖方法：（a）改变介质成分；（b）调节操作条件，例如pH和温度；或（c）通过从分批补料转为连​​续工艺来加强工艺操作。