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.