Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Automated quality analysis in continuous downstream processes for small-scale applications

Tallvod, Simon LU ; Espinoza, Daniel LU ; Gomis-Fons, Joaquín LU ; Andersson, Niklas LU orcid and Nilsson, Bernt LU (2023) In Journal of chromatography. A 1702.
Abstract
Development of integrated, continuous biomanufacturing (ICB) processes brings along the challenge of streamlining the acquisition of data that can be used for process monitoring, product quality testing and process control. Manually performing sample acquisition, preparation, and analysis during process and product development on ICB platforms requires time and labor that diverts attention from the development itself. It also introduces variability in terms of human error in the handling of samples. To address this, a platform for automatic sampling, sample preparation and analysis for use in small-scale biopharmaceutical downstream processes was developed. The automatic quality analysis system (QAS) consisted of an ÄKTA Explorer... (More)
Development of integrated, continuous biomanufacturing (ICB) processes brings along the challenge of streamlining the acquisition of data that can be used for process monitoring, product quality testing and process control. Manually performing sample acquisition, preparation, and analysis during process and product development on ICB platforms requires time and labor that diverts attention from the development itself. It also introduces variability in terms of human error in the handling of samples. To address this, a platform for automatic sampling, sample preparation and analysis for use in small-scale biopharmaceutical downstream processes was developed. The automatic quality analysis system (QAS) consisted of an ÄKTA Explorer chromatography system for sample retrieval, storage, and preparation, as well as an Agilent 1260 Infinity II analytical HPLC system for analysis. The ÄKTA Explorer system was fitted with a superloop in which samples could be stored, conditioned, and diluted before being sent to the injection loop of the Agilent system. The Python-based software Orbit, developed at the department of chemical engineering at Lund university, was used to control and create a communication framework for the systems.

To demonstrate the QAS in action, a continuous capture chromatography process utilizing periodic counter-current chromatography was set up on an ÄKTA Pure chromatography system to purify the clarified harvest from a bioreactor for monoclonal antibody production. The QAS was connected to the process to collect two types of samples: 1) the bioreactor supernatant and 2) the product pool from the capture chromatography. Once collected, the samples were conditioned and diluted in the superloop before being sent to the Agilent system, where both aggregate content and charge variant composition were determined using size-exclusion and ion-exchange chromatography, respectively. The QAS was successfully implemented during a continuous run of the capture process, enabling the acquisition of process data with consistent quality and without human intervention, clearing the path for automated process monitoring and data-based control. (Less)
Please use this url to cite or link to this publication:
author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of chromatography. A
volume
1702
article number
464085
pages
10 pages
publisher
Elsevier
external identifiers
  • scopus:85162267795
  • pmid:37245353
ISSN
1873-3778
DOI
10.1016/j.chroma.2023.464085
language
English
LU publication?
yes
id
3573d5ba-31c3-40d2-b6be-4404e3b54c6c
date added to LUP
2023-06-07 14:00:15
date last changed
2023-12-21 13:15:29
@article{3573d5ba-31c3-40d2-b6be-4404e3b54c6c,
  abstract     = {{Development of integrated, continuous biomanufacturing (ICB) processes brings along the challenge of streamlining the acquisition of data that can be used for process monitoring, product quality testing and process control. Manually performing sample acquisition, preparation, and analysis during process and product development on ICB platforms requires time and labor that diverts attention from the development itself. It also introduces variability in terms of human error in the handling of samples. To address this, a platform for automatic sampling, sample preparation and analysis for use in small-scale biopharmaceutical downstream processes was developed. The automatic quality analysis system (QAS) consisted of an ÄKTA Explorer chromatography system for sample retrieval, storage, and preparation, as well as an Agilent 1260 Infinity II analytical HPLC system for analysis. The ÄKTA Explorer system was fitted with a superloop in which samples could be stored, conditioned, and diluted before being sent to the injection loop of the Agilent system. The Python-based software Orbit, developed at the department of chemical engineering at Lund university, was used to control and create a communication framework for the systems.<br/><br/>To demonstrate the QAS in action, a continuous capture chromatography process utilizing periodic counter-current chromatography was set up on an ÄKTA Pure chromatography system to purify the clarified harvest from a bioreactor for monoclonal antibody production. The QAS was connected to the process to collect two types of samples: 1) the bioreactor supernatant and 2) the product pool from the capture chromatography. Once collected, the samples were conditioned and diluted in the superloop before being sent to the Agilent system, where both aggregate content and charge variant composition were determined using size-exclusion and ion-exchange chromatography, respectively. The QAS was successfully implemented during a continuous run of the capture process, enabling the acquisition of process data with consistent quality and without human intervention, clearing the path for automated process monitoring and data-based control.}},
  author       = {{Tallvod, Simon and Espinoza, Daniel and Gomis-Fons, Joaquín and Andersson, Niklas and Nilsson, Bernt}},
  issn         = {{1873-3778}},
  language     = {{eng}},
  month        = {{08}},
  publisher    = {{Elsevier}},
  series       = {{Journal of chromatography. A}},
  title        = {{Automated quality analysis in continuous downstream processes for small-scale applications}},
  url          = {{http://dx.doi.org/10.1016/j.chroma.2023.464085}},
  doi          = {{10.1016/j.chroma.2023.464085}},
  volume       = {{1702}},
  year         = {{2023}},
}