Sources and upstream processing - Pharmaceutical Biotechnology: Concepts and Aapplications - page 128

Ports, for e.g. pH probes,
thermometer, etc.

Ports

Baffle

Impeller Marine type

impeller

Air/gas sparger Air/gas sparger

(a)

(b)

Figure 5.9 Design of a generalized microbial cell fermentation vessel (a) and an animal cell bioreactor (b).
Animal cell bioreactors display several structural differences compared with microbial fermentation vessels.
Note in particular: (i) the use of a marine-type impeller (some animal cell bioreactors-air lift fermenters-are
devoid of impellers and use sparging of air-gas as the only means of media agitation); (ii) the absence of baf-
fl es; (iii) curved internal surfaces at the bioreactor base. These modifi cations aim to minimize damage to the
fragile animal cells during culture. Note that various additional bioreactor confi gurations are also commercially
available. Reprinted with permission from Proteins; Biochemistry and Biotechnology (2002), J. Wiley & Sons

from simple defi ned media (usually glucose and some mineral salts) to more complex media using
yeast extract and peptone. Choice of media depends upon factors such as:

• Exact nutrient requirements of producer cell line to maximize cell growth and product production.

• Economics (total media cost).

• Extracellular or intracellular nature of product. If the biopharmaceutical is an extracellular

product then the less complex the media composition the better, in order to render subsequent
product purifi cation as straightforward as possible.

Fermentation follows for several days subsequent to inoculation with the production-scale starter
culture ( Figure 5.7). During this process, biomass (i.e. cell mass) accumulates. In most cases, prod-
uct accumulates intracellularly and cells are harvested when maximum biomass yields are achieved.
This 'feed batch' approach is the one normally taken during biopharmaceutical manufacture, al-
though reactors can also be operated on a continuous basis, where fresh nutrient media is con-
tinually added and a fraction of the media/biomass continually removed and processed. During