Development of an integrated platform for the production of recombinant biopharmaceuticals

harma industry currently works on shortening the time required to manufacture
drug candidates to support early preclinical testing, and reduces the failure rate by
early screening of the molecules with the best potential to reach the market later
on. This thesis focused on the development and integration of three aspects of
manufacturing to contribute in achieving these objectives. The �rst one looked
at the way to approach experimentation. The use of DOE was generalised to the
whole development and the creation of a library of statistical tools to develop an
algorithm for the analysis of the commonly used Central composite and Box-Behnken
designs. This algorithm proved to be as e�cient as commercially available statistical
softwares but presents the advantage of automating the analysis of the DOE designs.
The second aspect consisted in developing viable manufacturing steps such as an
upstream PEI-mediated transfection process in CHO cells, capable of generating
100mg L-1 of product in less than 15 days, or a cation exchange puri�cation platform
using a Quality by Design approach. The third aspect focused on the integration of
di�erent processing steps to yield a whole integrated platform for the production,
then puri�cation of one gram of a reporter antibody. This platform proved to be
a cost e�ective alternative to the development of a stable producing cell clone for
the production of recombinant product. In addition, this research reveals that the
adoption of a statistically driven approach to process development is as important
as the implementation of innovative technologies to address the challenges ahead.