The manufacturing of recombinant protein is traditionally undertaken in mammalian cell culture. Today, speed, cost and safety are the primary considerations for process improvements in both upstream and downstream manufacturing. Leaders in the biopharmaceutical industry are striving for continuous improvements to increase throughput, lower costs and produce safer more efficacious drugs. This can be achieved through advances in cell line engineering, process development of cell culture, development of chemically defined media and increased emphasis on product characterization. In the first part, this review provides a historical perspective on approved biotherapeutics by regulatory bodies which pave the way for next-generation products (including gene therapy). In the second part, it focuses on the application of in vitro and in vivo cell line engineering approaches, modern process development improvements including continuous manufacturing, recent developments in media formulation, and improvements in critical quality attribute determinations for products produced predominantly in mammalian cells.

重组蛋白的生产传统上是在哺乳动物细胞培养中进行的。如今，速度，成本和安全性是上游和下游制造过程改进的主要考虑因素。生物制药行业的领导者正在努力进行持续改进，以提高通量，降低成本并生产更安全，更有效的药物。这可以通过细胞系工程技术的进步，细胞培养过程的发展，化学成分确定的培养基的发展以及对产物表征的日益重视来实现。在第一部分中，本综述提供了有关监管机构批准的生物疗法的历史观点，这些机构为下一代产品（包括基因疗法）铺平了道路。在第二部分中，重点介绍了体外应用以及体内细胞系工程方法，包括连续生产在内的现代工艺开发改进，培养基配方的最新开发以及对主要在哺乳动物细胞中生产的产品的关键质量属性确定的改进。