Process economy effects of modernizations in vaccine purification
June 12-17, 2016
The vaccine industry is currently modernizing old legacy processes. Old purification steps are being made obsolete by introducing modern purification techniques, aiming for increased quality and production efficiency at the same time as reducing cost. One approach to increase safety and productivity is to use closed single-use (SU) processing systems, preferably in combination with more modern separation principles.
Size exclusion chromatography (SEC) is a technique traditionally used for reduction of contaminant levels in vaccine processes and is suitable for purification of large molecules such as viruses. However, as the sample load in SEC is typically only 5% of the column volume, a built-in disadvantage is that very large columns will be required in production scale which is both challenging and expensive. Additionally, today such column size requirements are not compatible with a closed SU system approach.
For a more efficient size separation of biomolecules, a different type of bioprocessing chromatography media called core beads has been developed. The core bead technology allows for dual functionality combining size separation with bind/elute chromatography. Viruses and other large entities pass outside the beads while contaminants (< Mr 700 000) penetrate the inert outer shell and bind to the ligands in the inner core.
To investigate the impact on the process economy of shifting from SEC to single-use core bead chromatography, laboratory experiments were performed and a calculation tool for the total cost of ownership was developed. As model system influenza virus produced in MDCK cells were used, although this strategy could also be applied to other viruses. Small scale experiments showed that performance in terms of hemagglutinin yield and host cell protein removal with both approaches were comparable. In terms of process economy, core bead chromatography in a SU approach presented significantly higher productivity, smaller footprint and reduced WFI consumption than SEC in all investigated scenarios.
Mia Bennemo, "Process economy effects of modernizations in vaccine purification" in "Vaccine Technology VI", Laura Palomares, UNAM, Mexico Manon Cox, Protein Sciences Corporation, USA Tarit Mukhopadhyay, University College London, UK Nathalie Garçon, BIOASTER Technology Research Institute, FR Eds, ECI Symposium Series, (2016). http://dc.engconfintl.org/vaccine_vi/74