Digital Twins for Continuous mRNA Production

The global coronavirus pandemic continues to restrict public life worldwide. An effective means of limiting the pandemic is vaccination. Messenger ribonucleic acid (mRNA) vaccines currently available on the market have proven to be a well-tolerated and effective class of vaccine against coronavirus...

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Autores principales:	Heribert Helgers, Alina Hengelbrock, Axel Schmidt, Jochen Strube
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mRNA SARS-CoV-2 vaccines digital twin quality by design process analytical technology Chemical technology TP1-1185 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/248bac1f7ea2484c9aeea8689d2854f2
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spelling	oai:doaj.org-article:248bac1f7ea2484c9aeea8689d2854f22021-11-25T18:50:57ZDigital Twins for Continuous mRNA Production10.3390/pr91119672227-9717https://doaj.org/article/248bac1f7ea2484c9aeea8689d2854f22021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9717/9/11/1967https://doaj.org/toc/2227-9717The global coronavirus pandemic continues to restrict public life worldwide. An effective means of limiting the pandemic is vaccination. Messenger ribonucleic acid (mRNA) vaccines currently available on the market have proven to be a well-tolerated and effective class of vaccine against coronavirus type 2 (CoV2). Accordingly, demand is presently outstripping mRNA vaccine production. One way to increase productivity is to switch from the currently performed batch to continuous <i>in vitro</i> transcription, which has proven to be a crucial material-consuming step. In this article, a physico-chemical model of <i>in vitro</i> mRNA transcription in a tubular reactor is presented and compared to classical batch and continuous <i>in vitro</i> transcription in a stirred tank. The three models are validated based on a distinct and quantitative validation workflow. Statistically significant parameters are identified as part of the parameter determination concept. Monte Carlo simulations showed that the model is precise, with a deviation of less than 1%. The advantages of continuous production are pointed out compared to batchwise <i>in vitro</i> transcription by optimization of the space–time yield. Improvements of a factor of 56 (0.011 µM/min) in the case of the continuously stirred tank reactor (CSTR) and 68 (0.013 µM/min) in the case of the plug flow reactor (PFR) were found.Heribert HelgersAlina HengelbrockAxel SchmidtJochen StrubeMDPI AGarticlemRNASARS-CoV-2vaccinesdigital twinquality by designprocess analytical technologyChemical technologyTP1-1185ChemistryQD1-999ENProcesses, Vol 9, Iss 1967, p 1967 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mRNA SARS-CoV-2 vaccines digital twin quality by design process analytical technology Chemical technology TP1-1185 Chemistry QD1-999
spellingShingle	mRNA SARS-CoV-2 vaccines digital twin quality by design process analytical technology Chemical technology TP1-1185 Chemistry QD1-999 Heribert Helgers Alina Hengelbrock Axel Schmidt Jochen Strube Digital Twins for Continuous mRNA Production
description	The global coronavirus pandemic continues to restrict public life worldwide. An effective means of limiting the pandemic is vaccination. Messenger ribonucleic acid (mRNA) vaccines currently available on the market have proven to be a well-tolerated and effective class of vaccine against coronavirus type 2 (CoV2). Accordingly, demand is presently outstripping mRNA vaccine production. One way to increase productivity is to switch from the currently performed batch to continuous <i>in vitro</i> transcription, which has proven to be a crucial material-consuming step. In this article, a physico-chemical model of <i>in vitro</i> mRNA transcription in a tubular reactor is presented and compared to classical batch and continuous <i>in vitro</i> transcription in a stirred tank. The three models are validated based on a distinct and quantitative validation workflow. Statistically significant parameters are identified as part of the parameter determination concept. Monte Carlo simulations showed that the model is precise, with a deviation of less than 1%. The advantages of continuous production are pointed out compared to batchwise <i>in vitro</i> transcription by optimization of the space–time yield. Improvements of a factor of 56 (0.011 µM/min) in the case of the continuously stirred tank reactor (CSTR) and 68 (0.013 µM/min) in the case of the plug flow reactor (PFR) were found.
format	article
author	Heribert Helgers Alina Hengelbrock Axel Schmidt Jochen Strube
author_facet	Heribert Helgers Alina Hengelbrock Axel Schmidt Jochen Strube
author_sort	Heribert Helgers
title	Digital Twins for Continuous mRNA Production
title_short	Digital Twins for Continuous mRNA Production
title_full	Digital Twins for Continuous mRNA Production
title_fullStr	Digital Twins for Continuous mRNA Production
title_full_unstemmed	Digital Twins for Continuous mRNA Production
title_sort	digital twins for continuous mrna production
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/248bac1f7ea2484c9aeea8689d2854f2
work_keys_str_mv	AT heriberthelgers digitaltwinsforcontinuousmrnaproduction AT alinahengelbrock digitaltwinsforcontinuousmrnaproduction AT axelschmidt digitaltwinsforcontinuousmrnaproduction AT jochenstrube digitaltwinsforcontinuousmrnaproduction
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Digital Twins for Continuous mRNA Production

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