ABSTRACT
Around the end of the 1970s it became apparent that cells could be cultivated in vitro on a large scale for the production of a wide range of human health products. Since then, studies aimed at defining the relevant environmental conditions needed for efficient cell proliferation in vitro have been increasingly carried out. This has motivated work on the development of chemically defined media and on the determination of optimal physicochemical conditions (pH, temperature, dissolved oxygen, etc.) for culturing cells for large-scale operations. As a practical consequence of these studies, several types of equipment to control environmental culture conditions have been developed, giving rise to the bioreactor systems currently used in the biopharmaceutical industry. To ensure adequate cell proliferation and product biosynthesis, bioreac-
tors have to meet the following requirements:
(i) control the acid-base equilibrium (pH) of the culture medium; (ii) control temperature; (iii) provide gas exchange to appropriately supply oxygen to the cells and
remove excess carbon dioxide; (iv) allow the supply of nutrients through the use of adequate formula-
tions of culture media; (v) supply enough surface for adhesion of cells, in the case of anchorage-
dependent cells; (vi) maintain aseptic conditions, avoiding contamination by microorgan-
isms, viruses, or other cells.
