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Distributed automated manufacturing of pluripotent stem cell products

Establishing how to effectively manufacture cell therapies is an industry-level problem. Decentralised manufacturing is of increasing importance, and its challenges are recognised by healthcare regulators with deviations and comparability issues receiving specific attention from them. This paper is...

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Autores principales: Shariatzadeh, Maryam, Chandra, Amit, Wilson, Samantha L, McCall, Mark J, Morizur, Lise, Lesueur, Léa, Chose, Olivier, Gepp, Michael M., Schulz, André, Neubauer, Julia C., Zimmermann, Heiko, Abranches, Elsa, Man, Jennifer, O’Shea, Orla, Stacey, Glyn, Hewitt, Zoe, Williams, David J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer London 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954896/
https://www.ncbi.nlm.nih.gov/pubmed/31983799
http://dx.doi.org/10.1007/s00170-019-04516-1
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author Shariatzadeh, Maryam
Chandra, Amit
Wilson, Samantha L
McCall, Mark J
Morizur, Lise
Lesueur, Léa
Chose, Olivier
Gepp, Michael M.
Schulz, André
Neubauer, Julia C.
Zimmermann, Heiko
Abranches, Elsa
Man, Jennifer
O’Shea, Orla
Stacey, Glyn
Hewitt, Zoe
Williams, David J
author_facet Shariatzadeh, Maryam
Chandra, Amit
Wilson, Samantha L
McCall, Mark J
Morizur, Lise
Lesueur, Léa
Chose, Olivier
Gepp, Michael M.
Schulz, André
Neubauer, Julia C.
Zimmermann, Heiko
Abranches, Elsa
Man, Jennifer
O’Shea, Orla
Stacey, Glyn
Hewitt, Zoe
Williams, David J
author_sort Shariatzadeh, Maryam
collection PubMed
description Establishing how to effectively manufacture cell therapies is an industry-level problem. Decentralised manufacturing is of increasing importance, and its challenges are recognised by healthcare regulators with deviations and comparability issues receiving specific attention from them. This paper is the first to report the deviations and other risks encountered when implementing the expansion of human pluripotent stem cells (hPSCs) in an automated three international site–decentralised manufacturing setting. An experimental demonstrator project expanded a human embryonal carcinoma cell line (2102Ep) at three development sites in France, Germany and the UK using the CompacT SelecT (Sartorius Stedim, Royston, UK) automated cell culture platform. Anticipated variations between sites spanned material input, features of the process itself and production system details including different quality management systems and personnel. Where possible, these were pre-addressed by implementing strategies including standardisation, cell bank mycoplasma testing and specific engineering and process improvements. However, despite such measures, unexpected deviations occurred between sites including software incompatibility and machine/process errors together with uncharacteristic contaminations. Many only became apparent during process proving or during the process run. Further, parameters including growth rate and viability discrepancies could only be determined post-run, preventing ‘live’ corrective measures. The work confirms the critical nature of approaches usually taken in Good Manufacturing Practice (GMP) manufacturing settings and especially emphasises the requirement for monitoring steps to be included within the production system. Real-time process monitoring coupled with carefully structured quality systems is essential for multiple site working including clarity of decision-making roles. Additionally, an over-reliance upon post-process visual microscopic comparisons has major limitations; it is difficult for non-experts to detect deleterious culture changes and such detection is slow.
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spelling pubmed-69548962020-01-23 Distributed automated manufacturing of pluripotent stem cell products Shariatzadeh, Maryam Chandra, Amit Wilson, Samantha L McCall, Mark J Morizur, Lise Lesueur, Léa Chose, Olivier Gepp, Michael M. Schulz, André Neubauer, Julia C. Zimmermann, Heiko Abranches, Elsa Man, Jennifer O’Shea, Orla Stacey, Glyn Hewitt, Zoe Williams, David J Int J Adv Manuf Technol Original Article Establishing how to effectively manufacture cell therapies is an industry-level problem. Decentralised manufacturing is of increasing importance, and its challenges are recognised by healthcare regulators with deviations and comparability issues receiving specific attention from them. This paper is the first to report the deviations and other risks encountered when implementing the expansion of human pluripotent stem cells (hPSCs) in an automated three international site–decentralised manufacturing setting. An experimental demonstrator project expanded a human embryonal carcinoma cell line (2102Ep) at three development sites in France, Germany and the UK using the CompacT SelecT (Sartorius Stedim, Royston, UK) automated cell culture platform. Anticipated variations between sites spanned material input, features of the process itself and production system details including different quality management systems and personnel. Where possible, these were pre-addressed by implementing strategies including standardisation, cell bank mycoplasma testing and specific engineering and process improvements. However, despite such measures, unexpected deviations occurred between sites including software incompatibility and machine/process errors together with uncharacteristic contaminations. Many only became apparent during process proving or during the process run. Further, parameters including growth rate and viability discrepancies could only be determined post-run, preventing ‘live’ corrective measures. The work confirms the critical nature of approaches usually taken in Good Manufacturing Practice (GMP) manufacturing settings and especially emphasises the requirement for monitoring steps to be included within the production system. Real-time process monitoring coupled with carefully structured quality systems is essential for multiple site working including clarity of decision-making roles. Additionally, an over-reliance upon post-process visual microscopic comparisons has major limitations; it is difficult for non-experts to detect deleterious culture changes and such detection is slow. Springer London 2019-12-04 2020 /pmc/articles/PMC6954896/ /pubmed/31983799 http://dx.doi.org/10.1007/s00170-019-04516-1 Text en © The Author(s) 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Shariatzadeh, Maryam
Chandra, Amit
Wilson, Samantha L
McCall, Mark J
Morizur, Lise
Lesueur, Léa
Chose, Olivier
Gepp, Michael M.
Schulz, André
Neubauer, Julia C.
Zimmermann, Heiko
Abranches, Elsa
Man, Jennifer
O’Shea, Orla
Stacey, Glyn
Hewitt, Zoe
Williams, David J
Distributed automated manufacturing of pluripotent stem cell products
title Distributed automated manufacturing of pluripotent stem cell products
title_full Distributed automated manufacturing of pluripotent stem cell products
title_fullStr Distributed automated manufacturing of pluripotent stem cell products
title_full_unstemmed Distributed automated manufacturing of pluripotent stem cell products
title_short Distributed automated manufacturing of pluripotent stem cell products
title_sort distributed automated manufacturing of pluripotent stem cell products
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954896/
https://www.ncbi.nlm.nih.gov/pubmed/31983799
http://dx.doi.org/10.1007/s00170-019-04516-1
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