Biopharmaceutical process development
Currently, the majority of biopharmaceuticals is produced in large scale animal cell cultures. The ever-increasing demand for these biopharmaceuticals requires highly productive bioprocesses and shorter development timelines. We have been studying the mechanisms underlying cell growth, cell metabolism and product formation to rationally develop and optimize production processes of recombinant proteins (including monoclonal antibodies), viral vectors for gene therapy and several viral vaccines. To support and fasten the different phases of bioprocess development at both upstream and downstream levels we have been developing several tools, namely:
- Recombinase-mediated cassette exchange systems in cell line development – e.g. target integration of the recombinant genes to prevent clones screening each time a new process needs to be developed.
- Tools for high-throughput screening in early-stage phases of bioprocess development - namely for clone screening and culture medium and feeding strategies optimization - using fluorescence-based methods coupled with chemometric techniques.
- Tools for real-time bioprocess monitoring - also important to meet PAT (Process Analytical Technology) requirements, which encourage biopharmaceutical companies to implement advanced real-time monitoring and control tools in manufacturing plants as a way to guarantee good quality product at the end of the process as well as to easy the regulatory approval process and increase regulatory flexibility with respect to post-approval manufacturing changes.
- Tools for rational development of downstream purification strategies - Fundamental studies using dynamic light scattering and surface plasmon resonance are undertaken to create a better understanding on the type of interactions between the different biopharmaceuticals and the matrices used in the purification train. Thermodynamic and mass transfer models have been developed to describe separation processes which then help the design of robust separations to deliver a predefined quality as regards yield, purity and productivity.