Large‐scale Production of Mammalian Cells and Their Products: Engineering Principles and Barriers to Scale‐up

TLDR

Mammalian cell products are medically valuable, yet large‑scale manufacturing remains cost‑inefficient. Implementing process control can markedly boost productivity of these products. Large‑scale production employs techniques such as microcarriers, artificial capillaries, tubular spiral film, and microencapsulation, which must be optimized and oxygen‑transfer issues addressed, and can be further improved by adjusting fed‑batch environmental parameters or by continuous medium perfusion to shift metabolism away from toxic waste production. Toxic waste accumulation hampers growth and productivity, but overcoming these barriers can substantially reduce the cost of producing mammalian‑cell‑derived products.

Abstract

Mammalian cell products have great medical and clinical importance, but to date, production methods employed to manufacture these products on a large scale are not as cost efficient as they could be. The implementation of process control would greatly improve the productivity of these products. Recently developed methods to produce cells on a large scale, such as microcarriers, artificial capillaries, tubular spiral film, and microencapsulation must be optimized, and the problem of oxygen transfer limitation must be solved. The accumulation of potentially toxic waste products can inhibit growth and reduce productivity. This effect can be reduced by either adjusting the environmental parameters of a fed-batch culture, so that the cell's metabolism is shifted away from producing these compounds, or by continually perfusing medium through the culture. If these technical barriers can be overcome, the cost of producing products derived from mammalian cells can be greatly reduced.