High-throughput process development for biopharmaceutical drug substances

Bhambure, Rahul; Kumar, K. Arun; Rathore, Anurag S.

doi:10.1016/j.tibtech.2010.12.001

Cited by 154 publications

(113 citation statements)

References 51 publications

Supporting

Mentioning

108

Contrasting

Order By: Relevance

“…High-throughput process development was used to screen separation conditions because it allows a large number of conditions to be tested in a short period of time while also pushing the failure limits of the process. 13,14 We performed HTPD experiments in a 96-well plate format to study the effects of load [NaCl], wash [NaCl] and wash CVs on the recovery and purity of mAb-X from the Butyl Sepharose HP resin. At this stage, we decided to switch the salt in the HIC buffer system from ammonium sulfate to sodium chloride.…”

Section: Resultsmentioning

confidence: 99%

Analytical characterization of a monoclonal antibody therapeutic reveals a three-light chain species that is efficiently removed using hydrophobic interaction chromatography

Wollacott

Casaz

Morin

et al. 2013

mAbs

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

Analytical characterization of a monoclonal antibody therapeutic reveals a three-light chain species that is efficiently removed using hydrophobic interaction chromatography

Wollacott

Casaz

Morin

et al. 2013

mAbs

View full text Add to dashboard Cite

show abstract

“…With respect to cell-line engineering, opting for media optimization considerably reduces development timelines and the complexity of product quality comparability considerations, which typically results from redevelopment of cell lines. High-throughput cell culture systems opened the door for testing many conditions simultaneously [266][267][268] . The technology developed for media optimization in 96-deepwell plates (96-DWP) fed-batch cultures 26,27,251 can also be applied for product quality modulation 25,64 .…”

Section: Introductionmentioning

confidence: 99%

Tailoring recombinant protein quality by rational media design

Brühlmann

Jordan

Hemberger³

et al. 2015

Biotechnology Progress

View full text Add to dashboard Cite

Clinical efficacy and safety of recombinant proteins are closely associated with their structural characteristics. The major quality attributes comprise glycosylation, charge variants (oxidation, deamidation, and C‐ & N‐terminal modifications), aggregates, low‐molecular‐weight species (LMW), and misincorporation of amino acids in the protein backbone. Cell culture media design has a great potential to modulate these quality attributes due to the vital role of medium in mammalian cell culture. The purpose of this review is to provide an overview of the way both classical cell culture medium components and novel supplements affect the quality attributes of recombinant therapeutic proteins expressed in mammalian hosts, allowing rational and high‐throughput optimization of mammalian cell culture media. A selection of specific and/or potent inhibitors and activators of oligosaccharide processing as well as components affecting multiple quality attributes are presented. Extensive research efforts in this field show the feasibility of quality engineering through media design, allowing to significantly modulate the protein function. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:615–629, 2015

show abstract

“…For most of the unit operations, the devices (e.g., filter plates from various manufacturers or chromatography columns [MediaScout RoboColumn; Atoll GmbH, Weingarten, Germany]) are scaled down to the 96-well format, or new magnetic microspheres (MagReSyn; ReSyn Biosciences [Pty] Ltd, Edenvale, South Africa) are developed for high-throughput separation applications. More unit operations are reviewed by Nfor et al, 13 Bhambure et al, 14 and Cramer and Holstein. 15 But automation approaches still seem to be limited to single steps such as protein purification 16 or parallel chromatography.…”

Section: Introductionmentioning

confidence: 99%

Robotic Platform for Parallelized Cultivation and Monitoring of Microbial Growth Parameters in Microwell Plates

et al. 2014

View full text Add to dashboard Cite

The enormous variation possibilities of bioprocesses challenge process development to fix a commercial process with respect to costs and time. Although some cultivation systems and some devices for unit operations combine the latest technology on miniaturization, parallelization, and sensing, the degree of automation in upstream and downstream bioprocess development is still limited to single steps. We aim to face this challenge by an interdisciplinary approach to significantly shorten development times and costs. As a first step, we scaled down analytical assays to the microliter scale and created automated procedures for starting the cultivation and monitoring the optical density (OD), pH, concentrations of glucose and acetate in the culture medium, and product formation in fed-batch cultures in the 96-well format. Then, the separate measurements of pH, OD, and concentrations of acetate and glucose were combined to one method. This method enables automated process monitoring at dedicated intervals (e.g., also during the night). By this approach, we managed to increase the information content of cultivations in 96-microwell plates, thus turning them into a suitable tool for high-throughput bioprocess development. Here, we present the flowcharts as well as cultivation data of our automation approach.

show abstract

High-throughput process development for biopharmaceutical drug substances

Cited by 154 publications

References 51 publications

Analytical characterization of a monoclonal antibody therapeutic reveals a three-light chain species that is efficiently removed using hydrophobic interaction chromatography

Analytical characterization of a monoclonal antibody therapeutic reveals a three-light chain species that is efficiently removed using hydrophobic interaction chromatography

Tailoring recombinant protein quality by rational media design

Robotic Platform for Parallelized Cultivation and Monitoring of Microbial Growth Parameters in Microwell Plates

Contact Info

Product

Resources

About