Continuous chromatography beyond affinity capture of monoclonal antibodies

The focus on process intensification and increased process control continues in the biopharmaceutical industry. The key driver is to reduce production costs, while maintaining product quality and throughput in the manufacturing of biopharmaceuticals. The introduction of continuous processing technologies has supported the industry in evaluating different approaches for continuous and/or hybrid solutions for up- and downstream processing. Continuous chromatography has the potential to increase chromatography resin capacity utilization, eliminate or minimize the need for intermediate hold-up steps, reduce equipment footprint and buffer consumption as well as introducing a higher degree of automation. The benefits from this can in turn have a positive impact on the process economy. The efforts in continuous chromatography in the industry so far have mainly been focusing on affinity capture of monoclonal antibodies (mAb) but the interest in exploring other applications is now increasing. In this poster, we will show the usage of periodic counter-current chromatography (PCC) in and beyond affinity chromatography mAb capture applications, for example in purification processes for viral vectors as well as plasma proteins. We will show examples of flow through applications, ion exchange- and size exclusion chromatography in a continuous mode

The use of dynamic control in periodic counter current chromatography

The interest for use of continuous processing in biotech downstream operations is rapidly growing, driven by the gains in productivity, product stability and reduced cost of goods. Continuous processing encompasses a range of different approaches and can relate to both single step operations as well as semi- to fully continuous processes. Improvements in equipment and hardware have now made several commercial systems for continuous chromatography available. As implementation of various strategies for continuous processing becomes more common, the demand/need for reliability in monitoring with existing hardware solutions is steadily increasing. Integration of process analytical technologies will be the determining factor for successful implementation at clinical/bioprocess scale. Periodic counter current chromatography as used by the ÄKTA™ pcc system is one technology enabling continuous processing. A key feature associated with operation of this system is the intrinsic ability supplied by the dynamic control function to automatically cope with variations related to fluctuations in feed compositions e.g. when using perfusion feed and/or changes in chromatographic media performance occur.The capacity of the embedded control strategy will be demonstrated by examples from affinity purification of monoclonal antibodies and human IgG using Protein A chromatographic media. This will include the ability of the dynamic control to adapt to varying product titer in the feed as well as varying the dynamic binding capacity of individual columns. Additionally, different applications involving both bind/elute as well as flow through modes of chromatography will be discussed

Continuous downstream processing of a monoclonal antibody using Periodic Counter Current Chromatography (PCC) and Straight Through Processing (STP)

There is an increased interest to perform process intensification in order to reduce costs and improve throughput in the development and production of monoclonal antibodies (MAbs). One solution to these demands can be to implement continuous or semi-continuous downstream processing. New emerging technologies such as periodic counter-current (PCC) chromatography and straight through processing (STP) are entering the market. Here, these two technologies were evaluated in a continuous three step chromatography MAb process. The capture step was performed with protein A media (resin) on a 3 column PCC chromatography system followed by two polishing steps which were connected in series with an in line conditioning step in between. The three step process was performed using MAb from fed-batch cell culture. Results will also be presented based on the purification of MAb from a perfusion cell culture using PCC setup for the capture step