Developing integrated downstream processes for next-generation biologics

Abstract: Manufacturing of biopharmaceuticals is a costly and time consuming process due to its inherent complexity and variability. The downstream process is the most expensive part and it involves multiple non-trivial steps. Continuous integrated manufacturing is a new concept that is encouraged by authorities. The advantages include uninterrupted operation, automation, consistent product quality, lower residence times and decreased capital and operational costs. Novel techniques and concepts require a holistic process understanding as well as a technical competence to implement them, and to do that, there are multiple practical challenges that must be overcome. There is a growing need to rapidly adjust to market demands and also to decrease costs as the industry gets increasingly competitive. The ability to adjust a facility or production line, to manufacture a variety of biopharmaceuticals, must be taken into consideration when developing integrated systems. It is also important to be aware of how to monitor critical quality attributes to properly ensure product quality. Another important attribute of integrated systems is intuitive and how easy to use they are.The aim of the thesis is to demonstrate, based on a selection of case studies, how some of the presented challenges can be overcome. The case studies have integrated systems that are flexible and have advanced process analytical technology. One of the papers in this thesis also focuses on the optimization of coupled columns sequences with the purpose of reducing costs. Overall, the results of this thesis shows the potential of continuous integrated designs for purification of biopharmaceuticals while simultaneously increasing both performance and product quality.