Best Technology Application – DOWNSTREAM
WINNER: Pall Life Sciences * Cadence Acoustic Separator
The Cadence Acoustic Separator is a scalable single-use technology for cell culture clarification using acoustophoretic separation from process development through to large-scale drug manufacturing. It provides a novel, low-impact method of suspension clarification, separating cells and cell debris from cell culture fluid rapidly and efficiently. And uniquely, the Cadence Acoustic Separator can provide scalable continuous clarification when directly linked to primary downstream capture chromatography.
The Cadence Acoustic Separator features five peristaltic pumps that enable the use of four Cadence Acoustic Chambers that use a low frequency acoustic wave to generate a 3 dimensional standing wave across a flow channel. Cell culture from a fed batch bioreactor enters the flow channel, and as the cells pass through the 3D standing wave they are trapped by the acoustic forces. The trapped cells migrate to the nodes of the standing wave, and begin to clump together till such time as their buoyancy decreases and they settle out of the suspension by gravity. The cells can then be removed. In fact, the Cadence Acoustic Separator allows the cells to be continuously removed in a closed system without centrifugation or primary depth filtration, thus streamlining this challenging step in the biologics manufacturing process within a small operating footprint.
Puridify * FibroSelect
FibroSelect adsorbents from Puridify have the potential to enable disposable product capture purification at industrial scale by vastly improving productivity. The unique high capacity, high flowrate properties the proprietary adsorbent dramatically reduces unit operation size relative to traditional packed beds. The ready-to-operate units reduce validation burden, improve process robustness and increase facility flexibility. Protein A FibroSelect can achieve purification productivities in excess of 450 grams of mAb purified/Litre adsorbent/hour using a single cartridge on standard equipment. This is compared to just 6-15g/L/h achievable with traditional packed beads. Using a “multi-cycle, single batch” mode of operation FibroSelect units have demonstrated an ability to match process critical quality attributes when cycled over 190 times with 3 minute run times (1 second residence times). With dynamic binding capacities of >30mg/mL and novel housing devices with optimised fluid flow regimes the buffer usage and product concentration concerns of high flowrate chromatography applications are alleviated.
The rapid growth of single use technologies is driven by various known processing considerations, with the obvious gap in being product capture purification technologies. FibroSelect offers the potential to address so many of the advancements identified as critical to the development of the biopharm industry supported by research and analysis from leading organisations.
Sanofi * Accelerated Seamless Antibody Purification (ASAP)
ASAP (Accelerated Seamless Antibody Purification) is a sanofi-owned platform for continuous purification of mAbs (patent pending). ASAP was developed in the Bioprocess Science and Technologies department (Sanofi Vitry sur Seine, France), enabling to run three chromatography steps in continuous mode with no holding time nor open phase, including virus inactivation. This means that a cell culture bulk containing the Monoclonal Antibody can be fully and continuously processed to obtain a pure Monoclonal Antibody batch without any human intervention, decreasing process duration, resin and buffer costs. Dynamic evolution of ASAP already includes the use of membrane chromatography instead of conventional resins leading further improvement of productivity.
The process simplification underlying ASAP has only one goal: bring the process to higher productivity while keeping the purification simple and independent from complex technologies that could be challenging for process robustness. A key benefit of the advantages of the ASAP process and the continuous processing is the elimination of non-added-value unit operations like adjustment of pH, molarity and protein concentration, intermediate filtration and storage. The second advantage is a shortened process cycle time to complete the entire purification in less than 3 hours. For these reasons, processing in a continuous mode with ASAP is an industrial graal.