Engineering Commons^™

Integrated Continuous Bioprocessing – Opportunities And Challenges, Mats Akesson, Martin Heitmann, Ditte Skipstrup, Peter Tiainen

Integrated Continuous Biomanufacturing II

We have developed an integrated continuous processing framework for end-to-end production of complex fragile proteins based on perfusion cultivation and automated multi-step purification [1,2,3]. Upstream, the integrated system consists of a stirred tank bioreactor with an ATF cell retention system. The clarified harvest directly enters an off-the-shelf ÄKTA chromatography system converted into a continuous purification unit. Two alternating capture columns precede an automated multi-step purification train with full flexibility and control of individual columns.

The integrated set-up enables compact automated bench-top factories converting cell culture media to purified protein in an efficient manner without intermediate storage. It provides monitoring of …

Strategy For Scaling Semi-Continuous Downstream And Integration Of Process Analytical Tools For Monoclonal Antibody Toxicology, Darshini Shah, Rebecca Chmielowski, Colette Cutler, Hong Li, David Roush, Nihal Tugcu

Integrated Continuous Biomanufacturing II

Currently, continuous processing for biologics is being pursued from a technology perspective in order to increase productivity and decrease cost of manufacture. Disruptive technologies, such as PCC (Periodic Counter-current Chromatography), have been researched extensively in order to reduce the bottleneck for the downstream capture chromatography step. However, there is extremely limited knowledge in how to scale these disruptive technologies for clinical and commercial manufacturing. In this presentation, we demonstrate a strategy for scaling and integration of a PCC capture step into a semi-continuous downstream process (Protein A chromatography-Viral inactivation-Filtration-Anion exchange chromatography). Harvest cell culture fluid (HCCF) feed streams ranging from …

Cell Culture Scale Translation From A 24-Well Single-Use Miniature Bioreactor And Subsequent Impact On Product And Broth Quality, John Betts, Franc Baganz, Gary Lye, Steve Warr, Gary Finka, Mark Uden

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

To accelerate cell culture process development, most companies have validated scale-down models of their pilot and manufacturing scale bioreactors. Advancing such mimics to even smaller scales requires the large scale engineering environment to be accurately recreated. Here we describe a single-use microwell methodology that accurately reproduces not only cell growth kinetics but also key attributes related to product quality and broth processability.

The μ24 miniature bioreactor system enables system level control of agitation (by orbital shaking), with individual well control of pH, DO and temperature. Two distinct plate types are investigated, allowing for either headspace or direct gas sparging. An …

Challenges Of Scale Down Model For Disposable Bioreactors: Case Studies On Growth & Product Quality Impacts, Jincai Li, Guangming Zhang, Huilin Zhu

Single-Use Technologies: Bridging Polymer Science to Biotechnology Applications

Despite wide-spread use of disposable bioreactors, there is a lack of well-established scale-down model for larger scale SUBs. Here we report a case of NS0 cell culture process transfer from 2000L stainless steel bioreactor (SST) to 2000L disposable bioreactor (SUB). Initial attempts in trying to grow the NS0 cells in the small scale 2D bags yielded non-satisfactory results, as growth was impacted by bag material type as well as by suppliers of the same bag material type. However, 3D bags of 50L and above proved to be supportive of the NS0 cell line growth.

Even for cell lines that do …