Influenza Vaccine Manufacturing: Effect of Inactivation, Splitting and Site of Manufacturing. Comparison of Influenza Vaccine Production Processes

The aim of this study was to evaluate the impact of different inactivation and splitting procedures on influenza vaccine product composition, stability and recovery to support transfer of process technology. Four split and two whole inactivated virus (WIV) influenza vaccine bulks were produced and c...

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Autores principales: Kon, Theone C., Onu, Adrian, Berbecila, Laurentiu, Lupulescu, Emilia, Ghiorgisor, Alina, Kersten, Gideon F., Cui, Yi-Qing, Amorij, Jean-Pierre, Van der Pol, Leo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4784929/
https://www.ncbi.nlm.nih.gov/pubmed/26959983
http://dx.doi.org/10.1371/journal.pone.0150700
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author Kon, Theone C.
Onu, Adrian
Berbecila, Laurentiu
Lupulescu, Emilia
Ghiorgisor, Alina
Kersten, Gideon F.
Cui, Yi-Qing
Amorij, Jean-Pierre
Van der Pol, Leo
author_facet Kon, Theone C.
Onu, Adrian
Berbecila, Laurentiu
Lupulescu, Emilia
Ghiorgisor, Alina
Kersten, Gideon F.
Cui, Yi-Qing
Amorij, Jean-Pierre
Van der Pol, Leo
author_sort Kon, Theone C.
collection PubMed
description The aim of this study was to evaluate the impact of different inactivation and splitting procedures on influenza vaccine product composition, stability and recovery to support transfer of process technology. Four split and two whole inactivated virus (WIV) influenza vaccine bulks were produced and compared with respect to release criteria, stability of the bulk and haemagglutinin recovery. One clarified harvest of influenza H3N2 A/Uruguay virus prepared on 25.000 fertilized eggs was divided equally over six downstream processes. The main unit operation for purification was sucrose gradient zonal ultracentrifugation. The inactivation of the virus was performed with either formaldehyde in phosphate buffer or with beta-propiolactone in citrate buffer. For splitting of the viral products in presence of Tween(®), either Triton(™) X-100 or di-ethyl-ether was used. Removal of ether was established by centrifugation and evaporation, whereas removal of Triton-X100 was performed by hydrophobic interaction chromatography. All products were sterile filtered and subjected to a 5 months real time stability study. In all processes, major product losses were measured after sterile filtration; with larger losses for split virus than for WIV. The beta-propiolactone inactivation on average resulted in higher recoveries compared to processes using formaldehyde inactivation. Especially ether split formaldehyde product showed low recovery and least stability over a period of five months.
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spelling pubmed-47849292016-03-23 Influenza Vaccine Manufacturing: Effect of Inactivation, Splitting and Site of Manufacturing. Comparison of Influenza Vaccine Production Processes Kon, Theone C. Onu, Adrian Berbecila, Laurentiu Lupulescu, Emilia Ghiorgisor, Alina Kersten, Gideon F. Cui, Yi-Qing Amorij, Jean-Pierre Van der Pol, Leo PLoS One Research Article The aim of this study was to evaluate the impact of different inactivation and splitting procedures on influenza vaccine product composition, stability and recovery to support transfer of process technology. Four split and two whole inactivated virus (WIV) influenza vaccine bulks were produced and compared with respect to release criteria, stability of the bulk and haemagglutinin recovery. One clarified harvest of influenza H3N2 A/Uruguay virus prepared on 25.000 fertilized eggs was divided equally over six downstream processes. The main unit operation for purification was sucrose gradient zonal ultracentrifugation. The inactivation of the virus was performed with either formaldehyde in phosphate buffer or with beta-propiolactone in citrate buffer. For splitting of the viral products in presence of Tween(®), either Triton(™) X-100 or di-ethyl-ether was used. Removal of ether was established by centrifugation and evaporation, whereas removal of Triton-X100 was performed by hydrophobic interaction chromatography. All products were sterile filtered and subjected to a 5 months real time stability study. In all processes, major product losses were measured after sterile filtration; with larger losses for split virus than for WIV. The beta-propiolactone inactivation on average resulted in higher recoveries compared to processes using formaldehyde inactivation. Especially ether split formaldehyde product showed low recovery and least stability over a period of five months. Public Library of Science 2016-03-09 /pmc/articles/PMC4784929/ /pubmed/26959983 http://dx.doi.org/10.1371/journal.pone.0150700 Text en © 2016 Kon et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kon, Theone C.
Onu, Adrian
Berbecila, Laurentiu
Lupulescu, Emilia
Ghiorgisor, Alina
Kersten, Gideon F.
Cui, Yi-Qing
Amorij, Jean-Pierre
Van der Pol, Leo
Influenza Vaccine Manufacturing: Effect of Inactivation, Splitting and Site of Manufacturing. Comparison of Influenza Vaccine Production Processes
title Influenza Vaccine Manufacturing: Effect of Inactivation, Splitting and Site of Manufacturing. Comparison of Influenza Vaccine Production Processes
title_full Influenza Vaccine Manufacturing: Effect of Inactivation, Splitting and Site of Manufacturing. Comparison of Influenza Vaccine Production Processes
title_fullStr Influenza Vaccine Manufacturing: Effect of Inactivation, Splitting and Site of Manufacturing. Comparison of Influenza Vaccine Production Processes
title_full_unstemmed Influenza Vaccine Manufacturing: Effect of Inactivation, Splitting and Site of Manufacturing. Comparison of Influenza Vaccine Production Processes
title_short Influenza Vaccine Manufacturing: Effect of Inactivation, Splitting and Site of Manufacturing. Comparison of Influenza Vaccine Production Processes
title_sort influenza vaccine manufacturing: effect of inactivation, splitting and site of manufacturing. comparison of influenza vaccine production processes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4784929/
https://www.ncbi.nlm.nih.gov/pubmed/26959983
http://dx.doi.org/10.1371/journal.pone.0150700
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