Microbial technologies for biotherapeutics production: Key tools for advanced biopharmaceutical process development and control.

Current trends in the biopharmaceutical market such as the diversification of therapies as well as the increasing time-to-market pressure will trigger the rethinking of bioprocess development and production approaches. Thereby, the importance of development time and manufacturing costs will increase, especially for microbial production. In the present review, we investigate three technological approaches which, to our opinion, will play a key role in the future of biopharmaceutical production. The first cornerstone of process development is the generation and effective utilization of platform knowledge. Building processes on well understood microbial and technological platforms allows to accelerate early-stage bioprocess development and to better condense this knowledge into multi-purpose technologies and applicable mathematical models. Second, the application of verified scale down systems and in silico models for process design and characterization will reduce the required number of large scale batches before dossier submission. Third, the broader availability of mathematical process models and the improvement of process analytical technologies will increase the applicability and acceptance of advanced control and process automation in the manufacturing scale. This will reduce process failure rates and subsequently cost of goods. Along these three aspects we give an overview of recently developed key tools and their potential integration into bioprocess development strategies.