Editorial on “Advances in downstream processing of biologics – Spectroscopy: An emerging process analytical technology” by Matthias Rüdt, Till Briskot and Jürgen Hubbuch

AbstractThe aim of this study was to semi-automate process analytics for the quantification of common impurities in downstream processing such as host cell DNA, host cell proteins and endotoxins using a commercial liquid handling station. By semi-automation, the work load to fully analyze the elution peak of a purification run was reduced by at least 2.41 h. The relative standard deviation of results among different operators over a time span of up to 6 months was at the best reduced by half, e.g. from 13.7 to 7.1% in dsDNA analysis. Automation did not improve the reproducibility of results produced by one operator but released time for data evaluation and interpretation or planning of experiments. Overall, semi-automation of process analytics reduced operator-specific influence on test results. Such robust and reproducible analytics is fundamental to establish process analytical technology and get downstream processing ready for Quality by Design approaches.

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Biomanufacturing process analytical technology (PAT) application for downstream processing: Using dissolved oxygen as an indicator of product quality for a protein refolding reaction

Biotechnology and Bioengineering ◽

10.1002/bit.22382 ◽

2009 ◽

Vol 104 (2) ◽

pp. 340-351 ◽

Cited By ~ 18

Author(s):

Shelly A. Pizarro ◽

Rachel Dinges ◽

Rachel Adams ◽

Ailen Sanchez ◽

Charles Winter

Keyword(s):

Dissolved Oxygen ◽

Product Quality ◽

Process Analytical Technology ◽

Protein Refolding ◽

Downstream Processing ◽

Analytical Technology

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Digital Twin for Lyophilization by Process Modeling in Manufacturing of Biologics

Processes ◽

10.3390/pr8101325 ◽

2020 ◽

Vol 8 (10) ◽

pp. 1325

Author(s):

Leon S. Klepzig ◽

Alex Juckers ◽

Petra Knerr ◽

Frank Harms ◽

Jochen Strube

Keyword(s):

Process Design ◽

Process Model ◽

Process Analytical Technology ◽

Downstream Processing ◽

Pilot Scale ◽

Digital Twin ◽

Physical Chemical ◽

Optimization And Control ◽

And Control ◽

Analytical Technology

Lyophilization stabilizes formulated biologics for storage, transport and application to patients. In process design and operation it is the link between downstream processing and with final formulation to fill and finish. Recent activities in Quality by Design (QbD) have resulted in approaches by regulatory authorities and the need to include Process Analytical Technology (PAT) tools. An approach is outlined to validate a predictive physical-chemical (rigorous) lyophilization process model to act quantitatively as a digital twin in order to allow accelerated process design by modeling and to further-on develop autonomous process optimization and control towards real time release testing. Antibody manufacturing is chosen as a typical example for actual biologics needs. Literature is reviewed and the presented procedure is exemplified to quantitatively and consistently validate the physical-chemical process model with aid of an experimental statistical DOE (design of experiments) in pilot scale.

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