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On-line monitoring of downstream bioprocesses
Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0001-9711-794X
2016 (English)In: CURRENT OPINION IN CHEMICAL ENGINEERING, ISSN 2211-3398, Vol. 14, p. 112-120Article in journal (Refereed) Published
Abstract [en]

Downstream bioprocessing can benefit significantly from using on-line monitoring methods for surveillance, control and optimisation. Timely information on critical operational and product quality parameters provided by on-line monitoring may contribute to high product quality, more efficient process operation and better production economy. Here, recent advances in analytical techniques and tools are critically reviewed and assessed based on their capability to meet typical needs and requirements in the biotechnology industry. Soft sensors, which merge the signals generated from on-line monitoring devices into mathematical models, are highlighted for accessing critical information in downstream processing.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD , 2016. Vol. 14, p. 112-120
National Category
Chemical Process Engineering
Identifiers
URN: urn:nbn:se:liu:diva-133391DOI: 10.1016/j.coche.2016.09.007ISI: 000388517100016OAI: oai:DiVA.org:liu-133391DiVA, id: diva2:1060061
Note

Funding Agencies|EU-Horizon 2020 Marie Curie ITN project BIORAPID [643056]; Linkoping University

Available from: 2016-12-27 Created: 2016-12-22 Last updated: 2019-09-25
In thesis
1. Monitoring of product variants in biopharmaceutical downstream processing: Mechanistic and data-driven modeling approaches
Open this publication in new window or tab >>Monitoring of product variants in biopharmaceutical downstream processing: Mechanistic and data-driven modeling approaches
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

During the manufacturing of biopharmaceuticals, a multistep purification strategy is employed to remove process-related impurities and product variants, to achieve high product quality, assuring patients’ safety. To guarantee that biopharmaceuticals are safe and to accomplish quality, strict policies were established by regulatory agencies as well as guiding principles, such as Quality by Design and process analytical technology. To make the manufacturing process economical, relatively high product yield and productivity are also desirable.

The removal of product variants often poses a challenge in downstream processing due to their structural similarity to the product resulting in similar behavior. One way of overcoming this issue is to employ additional monitoring tools capable to distinguish between the product and product variants.

This thesis demonstrates the development of novel monitoring tools, based on existing monitoring and modeling approaches, to facilitate downstream processing.

Existing techniques are evaluated and critically compared toward meeting the requirements on monitoring quality attributes in downstream processing.

A mechanistic model-based monitoring tool was established for a reversed phase chromatography polishing step of insulin to predict the elution profile of insulin and two insulin variants. By relying on model-based monitoring a significant increase in product yield was achieved.

Further, multi-wavelength fluorescence spectroscopy coupled with the multi-way algorithm parallel factor analysis was utilized to monitor product variants of biopharmaceuticals in downstream processing. This monitoring tool capitalizes on a shift in fluorescence emission between the product and its variant. Developed for monitoring aggregates during antibody purification, the transferability of the approach to other relevant biopharmaceuticals, such as factor VIII and erythropoietin, has been confirmed.

The monitoring tools developed in this thesis, extend existing monitoring tools for downstream processing of biopharmaceuticals. When implementing these monitoring tools into the different phases of biopharmaceuticals’ lifespan, their potential could range from optimizing downstream processes during purification strategy development to supporting manufacturing by facilitating process decisions.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2019. p. 69
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 2010
National Category
Bioprocess Technology
Identifiers
urn:nbn:se:liu:diva-160524 (URN)10.3384/diss.diva-160524 (DOI)9789176850022 (ISBN)
Public defence
2019-10-25, Planck, F Building, Campus Valla, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2019-09-25 Created: 2019-09-25 Last updated: 2019-09-30Bibliographically approved

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