Entity

Time filter

Source Type


Hammerschmidt N.,University of Natural Resources and Life Sciences, Vienna | Hammerschmidt N.,Austria Center for Industrial Biotechnology | Tscheliessnig A.,University of Natural Resources and Life Sciences, Vienna | Sommer R.,University of Natural Resources and Life Sciences, Vienna | And 3 more authors.
Biotechnology Journal | Year: 2014

Standard industry processes for recombinant antibody production employ protein A affinity chromatography in combination with other chromatography steps and ultra-/diafiltration. This study compares a generic antibody production process with a recently developed purification process based on a series of selective precipitation steps. The new process makes two of the usual three chromatographic steps obsolete and can be performed in a continuous fashion. Cost of Goods (CoGs) analyses were done for: (i) a generic chromatography-based antibody standard purification; (ii) the continuous precipitation-based purification process coupled to a continuous perfusion production system; and (iii) a hybrid process, coupling the continuous purification process to an upstream batch process. The results of this economic analysis show that the precipitation-based process offers cost reductions at all stages of the life cycle of a therapeutic antibody, (i.e. clinical phase I, II and III, as well as full commercial production). The savings in clinical phase production are largely attributed to the fact that expensive chromatographic resins are omitted. These economic analyses will help to determine the strategies that are best suited for small-scale production in parallel fashion, which is of importance for antibody production in non-privileged countries and for personalized medicine. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Hammerschmidt N.,University of Natural Resources and Life Sciences, Vienna | Hammerschmidt N.,Austria Center for Industrial Biotechnology | Hintersteiner B.,University of Natural Resources and Life Sciences, Vienna | Lingg N.,University of Natural Resources and Life Sciences, Vienna | And 2 more authors.
Biotechnology Journal | Year: 2015

We successfully transferred a two-stage batch precipitation-based antibody capture step to continuous mode using continuous tubular reactors. The precipitation process solely employs a cheap mineral salt (CaCl2) and an organic solvent (ethanol) and could replace the costly protein A capture step in the purification of recombinant antibodies from cell culture supernatant. The time from startup untill attaining steady state conditions was reached in less than 15 minutes and both reactors were operated for several hours at steady state without manual intervention, delivering antibody at a constant yield and purity. An overall yield of > 90 percent, with a host cell protein reduction from 42777 to 9000 ppm and a DNA reduction from 359 ppm to 7 ppm, could be achieved for the antibody investigated. The precipitated antibody can be dissolved at very high concentrations (> 40 g/L) in numerous buffer systems of various pH and high and low ionic strength, thereby rendering a subsequent concentration or buffer exchange step redundant. This system enables cell culture supernatants with low or high antibody titer to be processed with constant reactor size and without changing any parameters or increasing precipitant consumption. Aggregate levels were below 1% under all conditions tested. Purification by precipitation did not affect binding to CD16a or the isoform distribution of the antibody. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Discover hidden collaborations