Biomedical Engineering Reference
In-Depth Information
34.
Biotechnol Adv
. 2008 Jan-Feb;
26(1):46-72. Epub 2007 Sep 19.
Upstream processes in antibody
production: evaluation of critical
parameters. Jain E, Kumar A.
Department of Biological
Sciences and Bioengineering,
Indian Institute of Technology
Kanpur, 208016-Kanpur, India.
The demand for monoclonal antibodies for
therapeutic and diagnostic applications is rising
constantly, which brings about a need to bring down
the cost of its production. In this context, it becomes
a prerequisite to improving the efficiency of the
existing processes used for monoclonal antibody
production. This review describes various upstream
processes used for monoclonal antibody production
and evaluates critical parameters and efforts that are
being made to enhance the efficiency of the process.
The upstream technology has been greatly upgraded
from host cells used for manufacturing to bioreactors
type and capacity. The host cells used a range from
microbial, mammalian, to plant cells, with
mammalian cells dominating the scenario.
Disposable bioreactors are being promoted for
small-scale production due to easy adaptation to
process validation and flexibility, though they are
limited by the scale of production. In this respect,
Wave Bioreactors for suspension culture have been
introduced recently. A novel bioreactor for
immobilized cells is described that permits an
economical and easy alternative to the hollow fiber
bioreactor at lab-scale production. Modification of
the cellular machinery to alter its metabolic
characteristics has further added to robustness of
cells and perks up cell specific productivity. The
process parameters, including feeding strategies and
environmental parameters, are being improved, and
efforts to validate them to get reproducible results
are becoming a trend. Online monitoring of the
process and product characterization is increasingly
gaining importance. In total, the advancement of
upstream processes have led to an increase in
volumetric productivity by 100-fold over the last
decade and make monoclonal antibody production a
more economical and realistic option for therapeutic
applications.
