Daniel Burgstaller, Walpurga Krepper, Josselyn Haas, Marine Maszelin, Jure Mohoric, Katja Pajnic, Alois Jungbauer and Peter Satzer, " Continuous cell flocculation for recombinant antibody harvesting." J Chem Technol Biotechnol 2018; 93: 1881–1890 DOI 10.1002/jctb.5500
Efficient, flexible and cost effective methods for continuous cell removal have to be developed before a fully continuous and integrated product train can be realized. The authors describe the development and testing of such an integrated continuous and disposable set-up for cell separation by flocculation combined with depth filtration.
ParticleTrack measurements were performed inline, after the addition of 0.0375% pDADMAC and positioned at the outlet of the tubular reactor (static-mixing). ParticleTrack (FBRM) monitors flocc size and when overlaid with time-resolved pressure, indicates the approach to filter saturation and trends with pressure events. The various methods and flocculant type evaluated resulted in different outcomes for total drug substance yield, purity, and High Molecular Weight Index (HMWI). These outcomes also showed correlation to divergent particle size distributions resulting from the chosen flocc type.
This data builds on previous publications showing correlation to other flocculation parameters such as flocc reagent concentration, mixing force or sheer, mixing resonance time, temperature, and starting condition and composition of whole cell broth. By using flocculation, the required depth filtration areas were successfully reduced by a factor of 4 compared with a conventional filtration train for which ParticleTrack (FBRM) was well suited to enable continuous antibody harvesting.