Sources and upstream processing - Pharmaceutical Biotechnology: Concepts and Aapplications - page 125

Figure 5.7 Outline of the upstream processing stages involved in the production of a single batch of prod-
uct. Initially, the contents of a single ampoule of the working cell bank (a) are used to inoculate a few hun-
dred millilitres of media (b). After growth, this laboratory-scale starter culture is used to inoculate several
litres/tens of litres of media present in a small bioreactor (c). This production-scale starter culture is used
to inoculate the production-scale bioreactor (d), which often contains several thousands/tens of thousands
litres of media. This process is equally applicable to prokaryotic or eukaryotic-based producer cell lines, al-
though the bioreactor design, conditions of growth, etc., will differ in these two instances
promote optimal cell growth/product production will have been established during initial product de-
velopment, and routine batch production is a highly repetitive, highly automated process. Bioreactors
are generally manufactured from high-grade stainless steel and can vary in size from a few tens of li-
tres to several tens of thousands of litres ( Figure 5.8). At the end of the production-scale fermentation
process, the crude product is harvested, which signals commencement of downstream processing.
Figure 5.8 Typical industrial-scale fermentation equipment as employed in the biopharmaceutical sector (a).
Control of the fermentation process is highly automated, with all fermentation parameters being adjusted by
computer (b). Photographs (a) and (b) courtesy of SmithKline Beecham Biological Services, s.a., Belgium. Photo-
graph (c) illustrates the inoculation of a laboratory-scale fermenter with recombinant microorganisms used in the
production of a commercial interferon preparation. Photograph (c) courtesy of Pall Life Sciences, Dublin, Ireland