A critical and expensive step involved in biomanufacturing is recovering highly pure samples efficiently from the biological source. The EU-funded INTENSO project identified bottlenecks in these downstream processing methods, and found solutions applicable to a wide range of products. Research concentrated on bioproducts that form part of most industrial research and development pipelines in order to reduce inefficiencies and costs. An integration/intensification strategy was proposed centred around four different methodologies for downstream processing technology: aqueous two-phase extraction (ATPE), expanded bed adsorption (EBA), convective flow systems (CFSs) and hybrid disposable cartridges (HDCs). The INTENSO team developed a variety of cell strains, bioproducts and upstream processes for ATPE. Applying pulsed electric fields to yeast and bacterial strains that produce different recombinant proteins has proven to facilitate the efficient release of bioproducts. Project partners evaluated the suitability of second-generation EBA to the primary recovery of products. This technology can be integrated very early in the bioprocessing scheme. As such, they investigated the effect of chemical coatings for the EBA process, providing a better process optimisation by minimising biomass-bead interactions. Experimental methods were developed and validated to characterise chromatographic beads. Scientists evaluated the performance of CFSs in capturing and purifying large biological molecules with great potential as future biopharmaceuticals, namely plasmid DNA, virus-like particles and messenger RNA. They showed that CFSs are almost ideal for purifying these molecules in terms of separation power, capacity and recovery, and molecule integrity. Radial chromatography enables the scale-up of chromatographic monoliths to industrial scale without compromising operation speed or separation efficiency. Lastly, the team used HDCs to generate a cost-effective and disposable system that supports eco-friendly bioprocessing. It produced protocols and sufficient materials of plasmid DNA, messenger RNA, recombinant proteins and monoclonal antibodies for further downstream processing. INTENSO significantly expanded current industrial downstream processing practices. European biotech companies that develop or adopt such technologies stand to benefit the most.
Biotech, bioproducts, downstream processing, INTENSO