Biomedical Engineering Reference
In-Depth Information
5
Disposable
Bioreactors
Piety is the fermentation of the forming mind and the putrefaction of the
disintegrating one
.
Franz Grillparzer (1791-1872), Austrian author
Notebooks and Diaries
(1838)
Hard-walled bioreactors have been used for centuries, from kitchen utensils
to multistory stainless steel behemoths; the field of bioreactor design has
remained pretty much the same for a long time. The essential elements of
a bioreactor—a utensil to contain a culture and media with sufficient mix-
ing and aeration—are readily provided in the traditional designs of bioreac-
tors. Today, we have a multitude of options in the design of bioreactors, and
these came about once the use of bioreactors expanded to the manufacture
of biological drugs requiring many control features that were not needed
or required in other industries. With the use of animal, human, and plant
cells and viruses to produce therapeutic proteins, vaccines, antibodies, etc.,
there arose a need to modify the traditional bioreactors to accommodate
the growth needs of these new production engines: recombinant engineer-
ing put these new engines in the forefront of biological drug production.
One major change in the design of bioreactors that is recent is the use of
disposable bioreactors to avoid the challenges of cleaning validation, thus
reducing the regulatory barriers in drug production. Hundreds of new mol-
ecules are under development using disposable bioreactors, and in many
instances disposable bioreactors are used to manufacture clinical supplies.
Yet, no drug has been approved for marketing that is manufactured on a
commercial scale using a disposable bioreactor. However, this situation will
soon change as the new molecules under development move further in the
approval cycle.
Almost all of recombinant drugs in the market today were developed
by large pharmaceutical companies starting about 30 years ago when the
only choice available was the traditional bioreactor; even though their pro-
cess may be less efficient, it is not worth the effort to switch over to another
manufacturing method because of the prohibitive cost of changeover pro-
tocols that need to be completed. A case in point is the use of roller bottles
to manufacture erythropoietin: Amgen, the world's largest producer of
erythropoietin, continues to use roller bottles despite their inefficiencies
and risks, but for new products Amgen will be using stirred bioreactors.
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