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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1782420328810545152 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4784929 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT kontheonec influenzavaccinemanufacturingeffectofinactivationsplittingandsiteofmanufacturingcomparisonofinfluenzavaccineproductionprocesses AT onuadrian influenzavaccinemanufacturingeffectofinactivationsplittingandsiteofmanufacturingcomparisonofinfluenzavaccineproductionprocesses AT berbecilalaurentiu influenzavaccinemanufacturingeffectofinactivationsplittingandsiteofmanufacturingcomparisonofinfluenzavaccineproductionprocesses AT lupulescuemilia influenzavaccinemanufacturingeffectofinactivationsplittingandsiteofmanufacturingcomparisonofinfluenzavaccineproductionprocesses AT ghiorgisoralina influenzavaccinemanufacturingeffectofinactivationsplittingandsiteofmanufacturingcomparisonofinfluenzavaccineproductionprocesses AT kerstengideonf influenzavaccinemanufacturingeffectofinactivationsplittingandsiteofmanufacturingcomparisonofinfluenzavaccineproductionprocesses AT cuiyiqing influenzavaccinemanufacturingeffectofinactivationsplittingandsiteofmanufacturingcomparisonofinfluenzavaccineproductionprocesses AT amorijjeanpierre influenzavaccinemanufacturingeffectofinactivationsplittingandsiteofmanufacturingcomparisonofinfluenzavaccineproductionprocesses AT vanderpolleo influenzavaccinemanufacturingeffectofinactivationsplittingandsiteofmanufacturingcomparisonofinfluenzavaccineproductionprocesses |