Annual Report 2006 - Boehringer Ingelheim

9
How innovations are made
The world of biopharmaceutical production has in the last five years grown
immensely due to ever-increasing market demand for monoclonal antibodies
(MAbs) and other therapeutic proteins. As many antibody-based therapies are
applied in high doses – for example in oncology – there is a need to ensure
high production capacity with high yield. Boehringer Ingelheim is meeting this
need by continuously improving biopharmaceutical production of therapeutics
derived from mammalian cell culture (Biberach, Germany) and bacterial
fermentation (Vienna, Austria). For gene therapeutics and DNA products
Boehringer Ingelheim’s expertise is increasingly in demand too.
At our biopharmaceutical site in Vienna we have
developed a fusion protein technology which uses
the bacteria E. coli to produce efficiently therapeutic
proteins. E. coli serves as a bacterial
expression system and core of a process which
ultimately delivers a therapeutic protein yield that
is four times that of current industrial standards.
This achievement will further strengthen the
company’s competitiveness in the area of produc-
tion of therapeutics of bacterial origin. Due to the
creativity and know-how of our teams in process
development and manufacturing, Boehringer
Ingelheim offers very economic, high-yield
processes performed in our modern facilities.
In 2000, Boehringer Ingelheim Austria entered
the area of plasmid DNA products, an important
therapeutic molecular structure which helps to
develop gene therapeutics and vaccines. During
the last five years, Boehringer Ingelheim has
advanced its plasmid DNA product yields from 50
mg/l to 2,000 mg/l – a 40-fold yield increase.
After the successful validation of the new Vienna
plant, Boehringer Ingelheim became the preferred
partner for the immediate uptake of late-stage and
commercial products to be produced in E. coli and
yeast. These include therapeutic proteins, antibody
fragments, protein scaffolds and plasmid
DNA products.
Boehringer Ingelheim A n n u A l R e p o R t 2 0 0 6
For some years now, Boehringer Ingelheim Pharma
in Biberach has had an international reputation
as a reliable contract developer and manufacturer
of biopharmaceuticals from mammalian cells and,
as such, has cultivated a long-standing and synergistic
relationship with highly respected companies
in the biopharmaceutical arena.
Recombinant proteins are manufactured by means
of fermentation in bioreactors. Cultivation depends
here on optimal conditions for cell growth and
production of the drug substance. The organisms
used (cell cultures or bacteria) are highly sensitive
to any changes such as temperature, pH, oxygen
and carbon dioxide saturation, length of the
process or excipients used. Biopharmaceutical
Process Development in Biberach tests and evaluates
at once the different cultivation conditions for
mammalian cell cultures (e.g. CHO cells) on a small
scale. These tests make it possible to determine the
optimal growth conditions for the cells which will
later be implemented in the large-scale bioreactors
for market production. This important part of
development is essential for the economic production
of drug substances with high-yield processes.