Biomedical Engineering Reference
In-Depth Information
20.
Adv Biochem Eng Biotechnol
. 2010;
115:1-31. Disposable bioreactors:
maturation into pharmaceutical
glycoprotein manufacturing.
Brecht R. ProBioGen AG,
Goethestrasse 54, Berlin,
Germany.
rene.brecht@
Modern biopharmaceutical development is
characterized by deep understanding of the
structure-activity relationship of biological drugs.
Therefore, the production process has to be tailored
more to the product requirements than to the existing
equipment in a certain facility. In addition, the major
challenges for the industry are to lower the high
production costs of biologics and to shorten the
overall development time. The flexibility for
providing different modes of operation using
disposable bioreactors in the same facility can fulfill
these demands and support tailor-made processes.
Over the last 10 years, a huge and still increasing
number of disposable bioreactors have entered the
market. Bioreactor volumes of up to 2,000 L can be
handled by using disposable bag systems. Each
individual technology has been made available for
different purposes up to the GMP compliant
production of therapeutic drugs, even for market
supply. This chapter summarizes disposable
technology development over the last decade by
comparing the different technologies and showing
trends and concepts for the future.
21.
Adv Biochem Eng Biotechnol
. 2010;
115:33-53. Use of orbital shaken
disposable bioreactors for
mammalian cell cultures from
the milliliter-scale to the
1,000-liter scale. Zhang X, Stettler
M, De Sanctis D, Perrone M,
Parolini N, Discacciati M, De
Jesus M, Hacker D, Quarteroni
A, Wurm F. Laboratory of
Cellular Biotechnology, Ecole
Polytechnique Fédérale de
Lausanne, CH-1015, Lausanne,
Switzerland.
Driven by the commercial success of recombinant
biopharmaceuticals, there is an increasing demand
for novel mammalian cell culture bioreactor systems
for the rapid production of biologicals that require
mammalian protein processing. Recently, orbitally
shaken bioreactors at scales from 50 mL to 1,000 L
have been explored for the cultivation of mammalian
cells and are considered to be attractive alternatives
to conventional stirred-tank bioreactors because of
increased flexibility and reduced costs. Adequate
oxygen transfer capacity was maintained during the
scale-up, and strategies to increase further oxygen
transfer rates (OTR) were explored, while
maintaining favorable mixing parameters and
low-stress conditions for sensitive lipid-membrane-
enclosed cells. Investigations from process
development to the engineering properties of shaken
bioreactors are under way, but the feasibility of
establishing a robust, standardized, and transferable
technical platform for mammalian cell culture based
on orbital shaking and disposable materials has been
established with further optimizations and studies
ongoing.
