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Quality by design modelling to support rapid RNA vaccine production against emerging infectious diseases

Rapid-response vaccine production platform technologies, including RNA vaccines, are being developed to combat viral epidemics and pandemics. A key enabler of rapid response is having quality-oriented disease-agnostic manufacturing protocols ready ahead of outbreaks. We are the first to apply the Qu...

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Autores principales: van de Berg, Damien, Kis, Zoltán, Behmer, Carl Fredrik, Samnuan, Karnyart, Blakney, Anna K., Kontoravdi, Cleo, Shattock, Robin, Shah, Nilay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085199/
https://www.ncbi.nlm.nih.gov/pubmed/33927197
http://dx.doi.org/10.1038/s41541-021-00322-7
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author van de Berg, Damien
Kis, Zoltán
Behmer, Carl Fredrik
Samnuan, Karnyart
Blakney, Anna K.
Kontoravdi, Cleo
Shattock, Robin
Shah, Nilay
author_facet van de Berg, Damien
Kis, Zoltán
Behmer, Carl Fredrik
Samnuan, Karnyart
Blakney, Anna K.
Kontoravdi, Cleo
Shattock, Robin
Shah, Nilay
author_sort van de Berg, Damien
collection PubMed
description Rapid-response vaccine production platform technologies, including RNA vaccines, are being developed to combat viral epidemics and pandemics. A key enabler of rapid response is having quality-oriented disease-agnostic manufacturing protocols ready ahead of outbreaks. We are the first to apply the Quality by Design (QbD) framework to enhance rapid-response RNA vaccine manufacturing against known and future viral pathogens. This QbD framework aims to support the development and consistent production of safe and efficacious RNA vaccines, integrating a novel qualitative methodology and a quantitative bioprocess model. The qualitative methodology identifies and assesses the direction, magnitude and shape of the impact of critical process parameters (CPPs) on critical quality attributes (CQAs). The mechanistic bioprocess model quantifies and maps the effect of four CPPs on the CQA of effective yield of RNA drug substance. Consequently, the first design space of an RNA vaccine synthesis bioreactor is obtained. The cost-yield optimization together with the probabilistic design space contribute towards automation of rapid-response, high-quality RNA vaccine production.
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spelling pubmed-80851992021-05-05 Quality by design modelling to support rapid RNA vaccine production against emerging infectious diseases van de Berg, Damien Kis, Zoltán Behmer, Carl Fredrik Samnuan, Karnyart Blakney, Anna K. Kontoravdi, Cleo Shattock, Robin Shah, Nilay NPJ Vaccines Article Rapid-response vaccine production platform technologies, including RNA vaccines, are being developed to combat viral epidemics and pandemics. A key enabler of rapid response is having quality-oriented disease-agnostic manufacturing protocols ready ahead of outbreaks. We are the first to apply the Quality by Design (QbD) framework to enhance rapid-response RNA vaccine manufacturing against known and future viral pathogens. This QbD framework aims to support the development and consistent production of safe and efficacious RNA vaccines, integrating a novel qualitative methodology and a quantitative bioprocess model. The qualitative methodology identifies and assesses the direction, magnitude and shape of the impact of critical process parameters (CPPs) on critical quality attributes (CQAs). The mechanistic bioprocess model quantifies and maps the effect of four CPPs on the CQA of effective yield of RNA drug substance. Consequently, the first design space of an RNA vaccine synthesis bioreactor is obtained. The cost-yield optimization together with the probabilistic design space contribute towards automation of rapid-response, high-quality RNA vaccine production. Nature Publishing Group UK 2021-04-29 /pmc/articles/PMC8085199/ /pubmed/33927197 http://dx.doi.org/10.1038/s41541-021-00322-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
van de Berg, Damien
Kis, Zoltán
Behmer, Carl Fredrik
Samnuan, Karnyart
Blakney, Anna K.
Kontoravdi, Cleo
Shattock, Robin
Shah, Nilay
Quality by design modelling to support rapid RNA vaccine production against emerging infectious diseases
title Quality by design modelling to support rapid RNA vaccine production against emerging infectious diseases
title_full Quality by design modelling to support rapid RNA vaccine production against emerging infectious diseases
title_fullStr Quality by design modelling to support rapid RNA vaccine production against emerging infectious diseases
title_full_unstemmed Quality by design modelling to support rapid RNA vaccine production against emerging infectious diseases
title_short Quality by design modelling to support rapid RNA vaccine production against emerging infectious diseases
title_sort quality by design modelling to support rapid rna vaccine production against emerging infectious diseases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085199/
https://www.ncbi.nlm.nih.gov/pubmed/33927197
http://dx.doi.org/10.1038/s41541-021-00322-7
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