Development of process analytical tools for rapid monitoring of live virus vaccines in manufacturing

In the development of end-to-end large-scale live virus vaccine (LVV) manufacturing, process analytical technology (PAT) tools enable timely monitoring of critical process parameters (CPP) and significantly guide process development and characterization. In a commercial setting, these very same tool...

Full description

Saved in:
Bibliographic Details
Published inScientific reports Vol. 12; no. 1; p. 15494
Main Authors Yi, Sijia, McCracken, Reilly, Davide, Joseph, Salovich, Daniel Ryan, Whitmer, Travis, Bhat, Aditya, Vlasak, Josef, Ha, Sha, Sehlin, Darrell, Califano, Joseph, Ploeger, Kristin, Mukherjee, Malini
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 15.09.2022
Nature Publishing Group
Nature Portfolio
Subjects
631/1647/2204
631/1647/245
631/1647/328
Acids
Bioreactors
Capacitance
Cell culture
Cell density
Flow cytometry
Genetic engineering
Glycoproteins
Humanities and Social Sciences
Infections
Manufacturing
Measles
Microscopy
Monitoring
multidisciplinary
Nanoparticles
Nucleic acids
Process controls
Proteins
Real time
Science
Science (multidisciplinary)
Vaccines
Vectors (Biology)
Viral infections
Viruses
Online AccessGet full text

Cover

Abstract In the development of end-to-end large-scale live virus vaccine (LVV) manufacturing, process analytical technology (PAT) tools enable timely monitoring of critical process parameters (CPP) and significantly guide process development and characterization. In a commercial setting, these very same tools can enable real time monitoring of CPPs on the shop floor and inform harvest decisions, predict peak potency, and serve as surrogates for release potency assays. Here we introduce the development of four advanced PAT tools for upstream and downstream process monitoring in LVV manufacturing. The first tool explores the application of capacitance probes for real time monitoring of viable cell density in bioreactors. The second tool utilizes high content imaging to determine optimum time of infection in a microcarrier process. The third tool uses flow virometry (or nanoscale flow cytometry) to monitor total virus particle counts across upstream and downstream process steps and establishes a robust correlation to virus potency. The fourth and final tool explores the use of nucleic acid dye staining to discriminate between “good” and “damaged” virus particles and uses this strategy to also monitor virus aggregates generated sometimes during downstream processing. Collectively, these tools provide a comprehensive monitoring toolbox and represent a significantly enhanced control strategy for the manufacturing of LVVs.
AbstractList In the development of end-to-end large-scale live virus vaccine (LVV) manufacturing, process analytical technology (PAT) tools enable timely monitoring of critical process parameters (CPP) and significantly guide process development and characterization. In a commercial setting, these very same tools can enable real time monitoring of CPPs on the shop floor and inform harvest decisions, predict peak potency, and serve as surrogates for release potency assays. Here we introduce the development of four advanced PAT tools for upstream and downstream process monitoring in LVV manufacturing. The first tool explores the application of capacitance probes for real time monitoring of viable cell density in bioreactors. The second tool utilizes high content imaging to determine optimum time of infection in a microcarrier process. The third tool uses flow virometry (or nanoscale flow cytometry) to monitor total virus particle counts across upstream and downstream process steps and establishes a robust correlation to virus potency. The fourth and final tool explores the use of nucleic acid dye staining to discriminate between “good” and “damaged” virus particles and uses this strategy to also monitor virus aggregates generated sometimes during downstream processing. Collectively, these tools provide a comprehensive monitoring toolbox and represent a significantly enhanced control strategy for the manufacturing of LVVs.
Abstract In the development of end-to-end large-scale live virus vaccine (LVV) manufacturing, process analytical technology (PAT) tools enable timely monitoring of critical process parameters (CPP) and significantly guide process development and characterization. In a commercial setting, these very same tools can enable real time monitoring of CPPs on the shop floor and inform harvest decisions, predict peak potency, and serve as surrogates for release potency assays. Here we introduce the development of four advanced PAT tools for upstream and downstream process monitoring in LVV manufacturing. The first tool explores the application of capacitance probes for real time monitoring of viable cell density in bioreactors. The second tool utilizes high content imaging to determine optimum time of infection in a microcarrier process. The third tool uses flow virometry (or nanoscale flow cytometry) to monitor total virus particle counts across upstream and downstream process steps and establishes a robust correlation to virus potency. The fourth and final tool explores the use of nucleic acid dye staining to discriminate between “good” and “damaged” virus particles and uses this strategy to also monitor virus aggregates generated sometimes during downstream processing. Collectively, these tools provide a comprehensive monitoring toolbox and represent a significantly enhanced control strategy for the manufacturing of LVVs.
Abstract In the development of end-to-end large-scale live virus vaccine (LVV) manufacturing, process analytical technology (PAT) tools enable timely monitoring of critical process parameters (CPP) and significantly guide process development and characterization. In a commercial setting, these very same tools can enable real time monitoring of CPPs on the shop floor and inform harvest decisions, predict peak potency, and serve as surrogates for release potency assays. Here we introduce the development of four advanced PAT tools for upstream and downstream process monitoring in LVV manufacturing. The first tool explores the application of capacitance probes for real time monitoring of viable cell density in bioreactors. The second tool utilizes high content imaging to determine optimum time of infection in a microcarrier process. The third tool uses flow virometry (or nanoscale flow cytometry) to monitor total virus particle counts across upstream and downstream process steps and establishes a robust correlation to virus potency. The fourth and final tool explores the use of nucleic acid dye staining to discriminate between “good” and “damaged” virus particles and uses this strategy to also monitor virus aggregates generated sometimes during downstream processing. Collectively, these tools provide a comprehensive monitoring toolbox and represent a significantly enhanced control strategy for the manufacturing of LVVs.
ArticleNumber 15494
Author Vlasak, Josef
Salovich, Daniel Ryan
Davide, Joseph
Bhat, Aditya
Sehlin, Darrell
Califano, Joseph
Mukherjee, Malini
Ha, Sha
Yi, Sijia
McCracken, Reilly
Whitmer, Travis
Ploeger, Kristin
Author_xml – sequence: 1
  givenname: Sijia
  surname: Yi
  fullname: Yi, Sijia
  organization: Vaccines Process Development and Commercialization, Merck & Co., Inc
– sequence: 2
  givenname: Reilly
  surname: McCracken
  fullname: McCracken, Reilly
  organization: Vaccines Process Development and Commercialization, Merck & Co., Inc
– sequence: 3
  givenname: Joseph
  surname: Davide
  fullname: Davide, Joseph
  organization: Vaccines Process Development and Commercialization, Merck & Co., Inc
– sequence: 4
  givenname: Daniel Ryan
  surname: Salovich
  fullname: Salovich, Daniel Ryan
  organization: Vaccines Process Development and Commercialization, Merck & Co., Inc
– sequence: 5
  givenname: Travis
  surname: Whitmer
  fullname: Whitmer, Travis
  organization: Vaccines Process Development and Commercialization, Merck & Co., Inc
– sequence: 6
  givenname: Aditya
  surname: Bhat
  fullname: Bhat, Aditya
  organization: Aber Instruments Inc
– sequence: 7
  givenname: Josef
  surname: Vlasak
  fullname: Vlasak, Josef
  organization: Vaccines Analytical Development, Merck & Co., Inc
– sequence: 8
  givenname: Sha
  surname: Ha
  fullname: Ha, Sha
  organization: Vaccines Process Development and Commercialization, Merck & Co., Inc
– sequence: 9
  givenname: Darrell
  surname: Sehlin
  fullname: Sehlin, Darrell
  organization: Vaccines Process Development and Commercialization, Merck & Co., Inc
– sequence: 10
  givenname: Joseph
  surname: Califano
  fullname: Califano, Joseph
  organization: Vaccines Process Development and Commercialization, Merck & Co., Inc
– sequence: 11
  givenname: Kristin
  surname: Ploeger
  fullname: Ploeger, Kristin
  organization: Vaccines Process Development and Commercialization, Merck & Co., Inc
– sequence: 12
  givenname: Malini
  surname: Mukherjee
  fullname: Mukherjee, Malini
  email: malini.mukherjee@merck.com
  organization: Vaccines Process Development and Commercialization, Merck & Co., Inc
BookMark eNp9kktv1TAQhSNUREvpH2BliQ2bgF-TxBskVF6VKrGBtTWxnYuvEjvYyVX77_G9qYCywBtbnnM-eTzneXUWYnBV9ZLRN4yK7m2WDFRXU85rplop67sn1QWnEmouOD_763xeXeW8p2UBV5KpZ9W5aBhVIMVFZT-4gxvjPLmwkDiQOUXjciYYcLxfvMGRLDGOmQwxkYSzt2SKwS8x-bA7GkZ_cOTg05rJAY3xwWXiA5kwrAOaZT3qXlRPBxyzu3rYL6vvnz5-u_5S3379fHP9_rY2wNqlxs72hgI2HTgzQKOsAMpsi4pR7FvVgGqHBrik1g3QCwALHRQDK0XaO3FZ3WxcG3Gv5-QnTPc6oteni5h2GlNpanTaNY5KpCAsoOwdqKHjg8ROcAOWOSysdxtrXvvJWVP-J-H4CPq4EvwPvYsHrWTbSM4L4PUDIMWfq8uLnnw2bhwxuLhmzVsGUgpQUKSv_pHu45rKBE4qWTpvTkC-qUyKOSc3_H4Mo_qYCb1lQpdM6FMm9F0xic2U5-MkXPqD_o_rFzL6vD4
CitedBy_id crossref_primary_10_1021_acs_oprd_3c00081
crossref_primary_10_1016_j_jbiotec_2024_01_016
crossref_primary_10_1002_bit_28703
crossref_primary_10_1016_j_biotechadv_2024_108391
Cites_doi 10.1021/ac201006u
10.1016/j.ymeth.2017.12.011
10.1172/JCI67042
10.1007/s00216-010-3781-x
10.3390/s150922128
10.1186/1743-422X-9-265
10.1038/s41541-021-00322-7
10.1038/nbt1261
10.1038/s41467-021-26506-2
10.1016/j.jpba.2021.114379
10.1016/j.vaccine.2017.06.003
10.1007/s00216-016-9492-1
10.1128/JVI.01765-17
10.1007/s00449-019-02216-4
10.3390/v14020383
10.1002/biot.201500184
10.1038/s41467-020-20228-7
10.1016/j.jvacx.2019.100009
10.1016/bs.pmbts.2014.10.012
10.1016/j.jbiotec.2015.07.001
10.1038/s41598-021-86688-z
10.1016/j.vaccine.2016.08.074
10.1002/btpr.2782
10.1002/biot.201800283
10.1016/j.virol.2014.06.005
10.4014/jmb.1004.04032
10.1007/s11095-010-0073-2
10.1016/0168-1656(92)90077-M
10.1002/bit.260430411
10.1016/j.jbiotec.2004.12.006
10.3949/ccjm.67.12.898
ContentType Journal Article
Copyright The Author(s) 2022
The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Copyright_xml – notice: The Author(s) 2022
– notice: The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
DBID C6C
AAYXX
CITATION
3V.
7X7
7XB
88A
88E
88I
8FE
8FH
8FI
8FJ
8FK
ABUWG
AFKRA
AZQEC
BBNVY
BENPR
BHPHI
CCPQU
DWQXO
FYUFA
GHDGH
GNUQQ
HCIFZ
K9.
LK8
M0S
M1P
M2P
M7P
PIMPY
PQEST
PQQKQ
PQUKI
Q9U
7X8
5PM
DOA
DOI 10.1038/s41598-022-19744-x
DatabaseName SpringerOpen
CrossRef
ProQuest Central (Corporate)
Health & Medical Collection (ProQuest Medical & Health Databases)
ProQuest Central (purchase pre-March 2016)
Biology Database (Alumni Edition)
Medical Database (Alumni Edition)
Science Database (Alumni Edition)
ProQuest SciTech Collection
ProQuest Natural Science Collection
Hospital Premium Collection
Hospital Premium Collection (Alumni Edition)
ProQuest Central (Alumni) (purchase pre-March 2016)
ProQuest Central (Alumni)
ProQuest Central
ProQuest Central Essentials
Biological Science Collection
AUTh Library subscriptions: ProQuest Central
ProQuest Natural Science Collection
ProQuest One Community College
ProQuest Central
Health Research Premium Collection
Health Research Premium Collection (Alumni)
ProQuest Central Student
SciTech Premium Collection (Proquest) (PQ_SDU_P3)
ProQuest Health & Medical Complete (Alumni)
Biological Sciences
Health & Medical Collection (Alumni Edition)
PML(ProQuest Medical Library)
ProQuest Science Journals
Biological Science Database
Access via ProQuest (Open Access)
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Academic
ProQuest One Academic UKI Edition
ProQuest Central Basic
MEDLINE - Academic
PubMed Central (Full Participant titles)
Directory of Open Access Journals
DatabaseTitle CrossRef
Publicly Available Content Database
ProQuest Central Student
ProQuest Central Essentials
ProQuest Health & Medical Complete (Alumni)
ProQuest Central (Alumni Edition)
SciTech Premium Collection
ProQuest One Community College
ProQuest Natural Science Collection
ProQuest Biology Journals (Alumni Edition)
ProQuest Central
Health Research Premium Collection
Health and Medicine Complete (Alumni Edition)
Natural Science Collection
ProQuest Central Korea
Biological Science Collection
ProQuest Medical Library (Alumni)
ProQuest Science Journals (Alumni Edition)
ProQuest Biological Science Collection
ProQuest Central Basic
ProQuest Science Journals
ProQuest One Academic Eastern Edition
ProQuest Hospital Collection
Health Research Premium Collection (Alumni)
Biological Science Database
ProQuest SciTech Collection
ProQuest Hospital Collection (Alumni)
ProQuest Health & Medical Complete
ProQuest Medical Library
ProQuest One Academic UKI Edition
ProQuest One Academic
ProQuest Central (Alumni)
MEDLINE - Academic
DatabaseTitleList Publicly Available Content Database
CrossRef
Database_xml – sequence: 1
  dbid: C6C
  name: SpringerOpen
  url: http://www.springeropen.com/
  sourceTypes: Publisher
– sequence: 2
  dbid: DOA
  name: Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 3
  dbid: BENPR
  name: AUTh Library subscriptions: ProQuest Central
  url: https://www.proquest.com/central
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Biology
EISSN 2045-2322
EndPage 15494
ExternalDocumentID oai_doaj_org_article_e6e04a053d5a4be59f82f4a832c5d1ea
10_1038_s41598_022_19744_x
GroupedDBID 0R~
3V.
4.4
53G
5VS
7X7
88A
88E
88I
8FE
8FH
8FI
8FJ
AAFWJ
AAJSJ
AAKDD
ABDBF
ABUWG
ACGFS
ACSMW
ADBBV
ADRAZ
AENEX
AFKRA
AJTQC
ALIPV
ALMA_UNASSIGNED_HOLDINGS
AOIJS
AZQEC
BAWUL
BBNVY
BCNDV
BENPR
BHPHI
BPHCQ
BVXVI
C6C
CCPQU
DIK
DWQXO
EBD
EBLON
EBS
ESX
FYUFA
GNUQQ
GROUPED_DOAJ
GX1
HCIFZ
HH5
HMCUK
HYE
KQ8
LK8
M0L
M1P
M2P
M48
M7P
M~E
NAO
OK1
PIMPY
PQQKQ
PROAC
PSQYO
RIG
RNT
RNTTT
RPM
SNYQT
UKHRP
AAYXX
AFPKN
CITATION
7XB
8FK
K9.
PQEST
PQUKI
Q9U
7X8
5PM
ID FETCH-LOGICAL-c517t-a8dbc05a685ecf569d3501d7a910ab796597f65240def5b355d58505a1b790be3
IEDL.DBID RPM
ISSN 2045-2322
IngestDate Tue Oct 22 14:51:54 EDT 2024
Tue Sep 17 21:15:25 EDT 2024
Fri Oct 25 00:41:12 EDT 2024
Fri Nov 08 21:56:11 EST 2024
Fri Aug 23 01:11:38 EDT 2024
Fri Oct 11 20:56:03 EDT 2024
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 1
Language English
License 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c517t-a8dbc05a685ecf569d3501d7a910ab796597f65240def5b355d58505a1b790be3
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
OpenAccessLink https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476422/
PMID 36109543
PQID 2714796622
PQPubID 2041939
PageCount 1
ParticipantIDs doaj_primary_oai_doaj_org_article_e6e04a053d5a4be59f82f4a832c5d1ea
pubmedcentral_primary_oai_pubmedcentral_nih_gov_9476422
proquest_miscellaneous_2715443595
proquest_journals_2714796622
crossref_primary_10_1038_s41598_022_19744_x
springer_journals_10_1038_s41598_022_19744_x
PublicationCentury 2000
PublicationDate 2022-09-15
PublicationDateYYYYMMDD 2022-09-15
PublicationDate_xml – month: 09
  year: 2022
  text: 2022-09-15
  day: 15
PublicationDecade 2020
PublicationPlace London
PublicationPlace_xml – name: London
PublicationTitle Scientific reports
PublicationTitleAbbrev Sci Rep
PublicationYear 2022
Publisher Nature Publishing Group UK
Nature Publishing Group
Nature Portfolio
Publisher_xml – name: Nature Publishing Group UK
– name: Nature Publishing Group
– name: Nature Portfolio
References Yahalom-Ronen (CR20) 2020; 11
van de Berg (CR1) 2021; 6
Gerzon, Sheng, Kirkitadze (CR8) 2022; 207
Lippé, Glaunsinger (CR15) 2018; 92
Ricci (CR27) 2021; 11
Austin, Watson, D'Amore (CR28) 1994; 43
Metze (CR33) 2020; 43
Klasse (CR26) 2015; 129
Ulmer, Valley, Rappuoli (CR6) 2006; 24
Daikoku, Morita, Kohno, Sano (CR24) 2007; 53
Heider, Metzner (CR7) 2014; 462–463
Moore, Sanford, Zhang (CR23) 2019; 35
Mironov (CR10) 2011; 83
Konakovsky (CR32) 2015; 15
Ferreira (CR30) 2005; 116
Monath (CR21) 2019; 1
CR4
Largoni (CR3) 2015; 211
Fernandes (CR22) 2019; 14
Zamora, Aguilar (CR14) 2018; 134–135
Frantz (CR19) 2021; 12
Fehrenbach, Comberbach, Petre (CR29) 1992; 23
Plotkin (CR5) 2017; 35
Rathore, Bhambure, Ghare (CR9) 2010; 398
Tang (CR18) 2016; 34
Grabherr, Reichl (CR2) 2015; 10
Ricci (CR17) 2021; 11
Bhat, Cao, Yin (CR25) 2022; 14
Knabben (CR31) 2011; 21
Arakelyan (CR16) 2013; 123
Kämmer (CR11) 2016; 408
Kramberger (CR13) 2012; 9
Filipe, Hawe, Jiskoot (CR12) 2010; 27
R Fehrenbach (19744_CR29) 1992; 23
19744_CR4
D van de Berg (19744_CR1) 2021; 6
JB Ulmer (19744_CR6) 2006; 24
G Gerzon (19744_CR8) 2022; 207
J Fernandes (19744_CR22) 2019; 14
I Knabben (19744_CR31) 2011; 21
G Ricci (19744_CR17) 2021; 11
A Arakelyan (19744_CR16) 2013; 123
PJ Klasse (19744_CR26) 2015; 129
AP Ferreira (19744_CR30) 2005; 116
R Grabherr (19744_CR2) 2015; 10
AS Rathore (19744_CR9) 2010; 398
GD Austin (19744_CR28) 1994; 43
T Bhat (19744_CR25) 2022; 14
B Moore (19744_CR23) 2019; 35
VA Tang (19744_CR18) 2016; 34
E Kämmer (19744_CR11) 2016; 408
JLR Zamora (19744_CR14) 2018; 134–135
GG Mironov (19744_CR10) 2011; 83
TP Monath (19744_CR21) 2019; 1
V Filipe (19744_CR12) 2010; 27
S Metze (19744_CR33) 2020; 43
R Lippé (19744_CR15) 2018; 92
PN Frantz (19744_CR19) 2021; 12
E Daikoku (19744_CR24) 2007; 53
P Kramberger (19744_CR13) 2012; 9
Y Yahalom-Ronen (19744_CR20) 2020; 11
M Largoni (19744_CR3) 2015; 211
V Konakovsky (19744_CR32) 2015; 15
S Heider (19744_CR7) 2014; 462–463
G Ricci (19744_CR27) 2021; 11
S Plotkin (19744_CR5) 2017; 35
References_xml – volume: 83
  start-page: 5431
  issue: 13
  year: 2011
  end-page: 5435
  ident: CR10
  article-title: Viral quantitative capillary electrophoresis for counting intact viruses
  publication-title: Anal. Chem.
  doi: 10.1021/ac201006u
  contributor:
    fullname: Mironov
– volume: 134–135
  start-page: 87
  year: 2018
  end-page: 97
  ident: CR14
  article-title: Flow virometry as a tool to study viruses
  publication-title: Methods
  doi: 10.1016/j.ymeth.2017.12.011
  contributor:
    fullname: Aguilar
– volume: 123
  start-page: 3716
  issue: 9
  year: 2013
  end-page: 3727
  ident: CR16
  article-title: Nanoparticle-based flow virometry for the analysis of individual virions
  publication-title: J. Clin. Investig.
  doi: 10.1172/JCI67042
  contributor:
    fullname: Arakelyan
– volume: 398
  start-page: 137
  issue: 1
  year: 2010
  end-page: 154
  ident: CR9
  article-title: Process analytical technology (PAT) for biopharmaceutical products
  publication-title: Anal. Bioanal. Chem.
  doi: 10.1007/s00216-010-3781-x
  contributor:
    fullname: Ghare
– volume: 15
  start-page: 22128
  issue: 9
  year: 2015
  end-page: 22150
  ident: CR32
  article-title: Universal capacitance model for real-time biomass in cell culture
  publication-title: Sensors (Basel)
  doi: 10.3390/s150922128
  contributor:
    fullname: Konakovsky
– volume: 9
  start-page: 265
  issue: 1
  year: 2012
  ident: CR13
  article-title: Evaluation of nanoparticle tracking analysis for total virus particle determination
  publication-title: Virol. J.
  doi: 10.1186/1743-422X-9-265
  contributor:
    fullname: Kramberger
– volume: 6
  start-page: 65
  issue: 1
  year: 2021
  ident: CR1
  article-title: Quality by design modelling to support rapid RNA vaccine production against emerging infectious diseases
  publication-title: NPJ Vaccines
  doi: 10.1038/s41541-021-00322-7
  contributor:
    fullname: van de Berg
– volume: 24
  start-page: 1377
  issue: 11
  year: 2006
  end-page: 1383
  ident: CR6
  article-title: Vaccine manufacturing: Challenges and solutions
  publication-title: Nat. Biotechnol.
  doi: 10.1038/nbt1261
  contributor:
    fullname: Rappuoli
– volume: 12
  start-page: 6277
  issue: 1
  year: 2021
  ident: CR19
  article-title: A live measles-vectored COVID-19 vaccine induces strong immunity and protection from SARS-CoV-2 challenge in mice and hamsters
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-021-26506-2
  contributor:
    fullname: Frantz
– volume: 207
  start-page: 114379
  year: 2022
  ident: CR8
  article-title: Process analytical technologies—Advances in bioprocess integration and future perspectives
  publication-title: J. Pharm. Biomed. Anal.
  doi: 10.1016/j.jpba.2021.114379
  contributor:
    fullname: Kirkitadze
– ident: CR4
– volume: 35
  start-page: 4064
  issue: 33
  year: 2017
  end-page: 4071
  ident: CR5
  article-title: The complexity and cost of vaccine manufacturing—An overview
  publication-title: Vaccine
  doi: 10.1016/j.vaccine.2017.06.003
  contributor:
    fullname: Plotkin
– volume: 408
  start-page: 4035
  issue: 15
  year: 2016
  end-page: 4041
  ident: CR11
  article-title: Single particle analysis of herpes simplex virus: Comparing the dimensions of one and the same virions via atomic force and scanning electron microscopy
  publication-title: Anal. Bioanal. Chem.
  doi: 10.1007/s00216-016-9492-1
  contributor:
    fullname: Kämmer
– volume: 92
  start-page: e01765
  issue: 3
  year: 2018
  end-page: e1817
  ident: CR15
  article-title: Flow virometry: A powerful tool to functionally characterize viruses
  publication-title: J. Virol.
  doi: 10.1128/JVI.01765-17
  contributor:
    fullname: Glaunsinger
– volume: 43
  start-page: 193
  issue: 2
  year: 2020
  end-page: 205
  ident: CR33
  article-title: Monitoring online biomass with a capacitance sensor during scale-up of industrially relevant CHO cell culture fed-batch processes in single-use bioreactors
  publication-title: Bioprocess Biosyst. Eng.
  doi: 10.1007/s00449-019-02216-4
  contributor:
    fullname: Metze
– volume: 14
  start-page: 383
  issue: 2
  year: 2022
  ident: CR25
  article-title: Virus-like particles: Measures and biological functions
  publication-title: Viruses
  doi: 10.3390/v14020383
  contributor:
    fullname: Yin
– volume: 10
  start-page: 657
  issue: 5
  year: 2015
  end-page: 658
  ident: CR2
  article-title: Editorial: Can modern vaccine technology pursue the success of traditional vaccine manufacturing?
  publication-title: Biotechnol. J.
  doi: 10.1002/biot.201500184
  contributor:
    fullname: Reichl
– volume: 11
  start-page: 6402
  issue: 1
  year: 2020
  ident: CR20
  article-title: A single dose of recombinant VSV-∆G-spike vaccine provides protection against SARS-CoV-2 challenge
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-020-20228-7
  contributor:
    fullname: Yahalom-Ronen
– volume: 1
  start-page: 100009
  year: 2019
  ident: CR21
  article-title: rVSVDeltaG-ZEBOV-GP (also designated V920) recombinant vesicular stomatitis virus pseudotyped with Ebola Zaire Glycoprotein: Standardized template with key considerations for a risk/benefit assessment
  publication-title: Vaccine X
  doi: 10.1016/j.jvacx.2019.100009
  contributor:
    fullname: Monath
– volume: 129
  start-page: 285
  year: 2015
  end-page: 326
  ident: CR26
  article-title: Molecular determinants of the ratio of inert to infectious virus particles
  publication-title: Prog. Mol. Biol. Transl. Sci.
  doi: 10.1016/bs.pmbts.2014.10.012
  contributor:
    fullname: Klasse
– volume: 211
  start-page: 87
  year: 2015
  end-page: 96
  ident: CR3
  article-title: Quality-by-design approach to monitor the operation of a batch bioreactor in an industrial avian vaccine manufacturing process
  publication-title: J. Biotechnol.
  doi: 10.1016/j.jbiotec.2015.07.001
  contributor:
    fullname: Largoni
– volume: 11
  start-page: 7432
  issue: 1
  year: 2021
  ident: CR17
  article-title: Flow virometry for process monitoring of live virus vaccines-lessons learned from ERVEBO
  publication-title: Sci. Rep.
  doi: 10.1038/s41598-021-86688-z
  contributor:
    fullname: Ricci
– volume: 34
  start-page: 5082
  issue: 42
  year: 2016
  end-page: 5089
  ident: CR18
  article-title: Single-particle characterization of oncolytic vaccinia virus by flow virometry
  publication-title: Vaccine
  doi: 10.1016/j.vaccine.2016.08.074
  contributor:
    fullname: Tang
– volume: 35
  start-page: e2782
  issue: 3
  year: 2019
  ident: CR23
  article-title: Case study: The characterization and implementation of dielectric spectroscopy (biocapacitance) for process control in a commercial GMP CHO manufacturing process
  publication-title: Biotechnol Prog
  doi: 10.1002/btpr.2782
  contributor:
    fullname: Zhang
– volume: 53
  start-page: 107
  issue: 2
  year: 2007
  end-page: 14
  ident: CR24
  article-title: Analysis of morphology and infectivity of measles virus particles
  publication-title: Bull. Osaka Med. Coll.
  contributor:
    fullname: Sano
– volume: 14
  start-page: e1800283
  issue: 4
  year: 2019
  ident: CR22
  article-title: Development of capacitance tools: At-line method for assessing biomass of mammalian cell culture and fixed cell calibration standard
  publication-title: Biotechnol. J.
  doi: 10.1002/biot.201800283
  contributor:
    fullname: Fernandes
– volume: 462–463
  start-page: 199
  year: 2014
  end-page: 206
  ident: CR7
  article-title: Quantitative real-time single particle analysis of virions
  publication-title: Virology
  doi: 10.1016/j.virol.2014.06.005
  contributor:
    fullname: Metzner
– volume: 21
  start-page: 204
  issue: 2
  year: 2011
  end-page: 211
  ident: CR31
  article-title: Linear correlation between online capacitance and offline biomass measurement up to high cell densities in fermentations in a pilot-scale pressurized bioreactor
  publication-title: J. Microbiol. Biotechnol.
  doi: 10.4014/jmb.1004.04032
  contributor:
    fullname: Knabben
– volume: 27
  start-page: 796
  issue: 5
  year: 2010
  end-page: 810
  ident: CR12
  article-title: Critical evaluation of Nanoparticle Tracking Analysis (NTA) by NanoSight for the measurement of nanoparticles and protein aggregates
  publication-title: Pharm. Res.
  doi: 10.1007/s11095-010-0073-2
  contributor:
    fullname: Jiskoot
– volume: 23
  start-page: 303
  issue: 3
  year: 1992
  end-page: 314
  ident: CR29
  article-title: On-line biomass monitoring by capacitance measurement
  publication-title: J. Biotechnol.
  doi: 10.1016/0168-1656(92)90077-M
  contributor:
    fullname: Petre
– volume: 43
  start-page: 337
  issue: 4
  year: 1994
  end-page: 341
  ident: CR28
  article-title: Studies of on-line viable yeast biomass with a capacitance biomass monitor
  publication-title: Biotechnol. Bioeng.
  doi: 10.1002/bit.260430411
  contributor:
    fullname: D'Amore
– volume: 116
  start-page: 403
  issue: 4
  year: 2005
  end-page: 409
  ident: CR30
  article-title: Evaluation of a new annular capacitance probe for biomass monitoring in industrial pilot-scale fermentations
  publication-title: J. Biotechnol.
  doi: 10.1016/j.jbiotec.2004.12.006
  contributor:
    fullname: Ferreira
– volume: 11
  start-page: 7432
  issue: 1
  year: 2021
  ident: CR27
  article-title: Flow virometry for process monitoring of live virus vaccines-lessons learned from ERVEBO
  publication-title: Sci. Rep.
  doi: 10.1038/s41598-021-86688-z
  contributor:
    fullname: Ricci
– volume: 12
  start-page: 6277
  issue: 1
  year: 2021
  ident: 19744_CR19
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-021-26506-2
  contributor:
    fullname: PN Frantz
– volume: 462–463
  start-page: 199
  year: 2014
  ident: 19744_CR7
  publication-title: Virology
  doi: 10.1016/j.virol.2014.06.005
  contributor:
    fullname: S Heider
– volume: 1
  start-page: 100009
  year: 2019
  ident: 19744_CR21
  publication-title: Vaccine X
  doi: 10.1016/j.jvacx.2019.100009
  contributor:
    fullname: TP Monath
– ident: 19744_CR4
  doi: 10.3949/ccjm.67.12.898
– volume: 11
  start-page: 7432
  issue: 1
  year: 2021
  ident: 19744_CR17
  publication-title: Sci. Rep.
  doi: 10.1038/s41598-021-86688-z
  contributor:
    fullname: G Ricci
– volume: 34
  start-page: 5082
  issue: 42
  year: 2016
  ident: 19744_CR18
  publication-title: Vaccine
  doi: 10.1016/j.vaccine.2016.08.074
  contributor:
    fullname: VA Tang
– volume: 43
  start-page: 193
  issue: 2
  year: 2020
  ident: 19744_CR33
  publication-title: Bioprocess Biosyst. Eng.
  doi: 10.1007/s00449-019-02216-4
  contributor:
    fullname: S Metze
– volume: 92
  start-page: e01765
  issue: 3
  year: 2018
  ident: 19744_CR15
  publication-title: J. Virol.
  doi: 10.1128/JVI.01765-17
  contributor:
    fullname: R Lippé
– volume: 14
  start-page: 383
  issue: 2
  year: 2022
  ident: 19744_CR25
  publication-title: Viruses
  doi: 10.3390/v14020383
  contributor:
    fullname: T Bhat
– volume: 10
  start-page: 657
  issue: 5
  year: 2015
  ident: 19744_CR2
  publication-title: Biotechnol. J.
  doi: 10.1002/biot.201500184
  contributor:
    fullname: R Grabherr
– volume: 24
  start-page: 1377
  issue: 11
  year: 2006
  ident: 19744_CR6
  publication-title: Nat. Biotechnol.
  doi: 10.1038/nbt1261
  contributor:
    fullname: JB Ulmer
– volume: 35
  start-page: 4064
  issue: 33
  year: 2017
  ident: 19744_CR5
  publication-title: Vaccine
  doi: 10.1016/j.vaccine.2017.06.003
  contributor:
    fullname: S Plotkin
– volume: 11
  start-page: 6402
  issue: 1
  year: 2020
  ident: 19744_CR20
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-020-20228-7
  contributor:
    fullname: Y Yahalom-Ronen
– volume: 43
  start-page: 337
  issue: 4
  year: 1994
  ident: 19744_CR28
  publication-title: Biotechnol. Bioeng.
  doi: 10.1002/bit.260430411
  contributor:
    fullname: GD Austin
– volume: 14
  start-page: e1800283
  issue: 4
  year: 2019
  ident: 19744_CR22
  publication-title: Biotechnol. J.
  doi: 10.1002/biot.201800283
  contributor:
    fullname: J Fernandes
– volume: 116
  start-page: 403
  issue: 4
  year: 2005
  ident: 19744_CR30
  publication-title: J. Biotechnol.
  doi: 10.1016/j.jbiotec.2004.12.006
  contributor:
    fullname: AP Ferreira
– volume: 11
  start-page: 7432
  issue: 1
  year: 2021
  ident: 19744_CR27
  publication-title: Sci. Rep.
  doi: 10.1038/s41598-021-86688-z
  contributor:
    fullname: G Ricci
– volume: 134–135
  start-page: 87
  year: 2018
  ident: 19744_CR14
  publication-title: Methods
  doi: 10.1016/j.ymeth.2017.12.011
  contributor:
    fullname: JLR Zamora
– volume: 207
  start-page: 114379
  year: 2022
  ident: 19744_CR8
  publication-title: J. Pharm. Biomed. Anal.
  doi: 10.1016/j.jpba.2021.114379
  contributor:
    fullname: G Gerzon
– volume: 83
  start-page: 5431
  issue: 13
  year: 2011
  ident: 19744_CR10
  publication-title: Anal. Chem.
  doi: 10.1021/ac201006u
  contributor:
    fullname: GG Mironov
– volume: 15
  start-page: 22128
  issue: 9
  year: 2015
  ident: 19744_CR32
  publication-title: Sensors (Basel)
  doi: 10.3390/s150922128
  contributor:
    fullname: V Konakovsky
– volume: 408
  start-page: 4035
  issue: 15
  year: 2016
  ident: 19744_CR11
  publication-title: Anal. Bioanal. Chem.
  doi: 10.1007/s00216-016-9492-1
  contributor:
    fullname: E Kämmer
– volume: 123
  start-page: 3716
  issue: 9
  year: 2013
  ident: 19744_CR16
  publication-title: J. Clin. Investig.
  doi: 10.1172/JCI67042
  contributor:
    fullname: A Arakelyan
– volume: 23
  start-page: 303
  issue: 3
  year: 1992
  ident: 19744_CR29
  publication-title: J. Biotechnol.
  doi: 10.1016/0168-1656(92)90077-M
  contributor:
    fullname: R Fehrenbach
– volume: 129
  start-page: 285
  year: 2015
  ident: 19744_CR26
  publication-title: Prog. Mol. Biol. Transl. Sci.
  doi: 10.1016/bs.pmbts.2014.10.012
  contributor:
    fullname: PJ Klasse
– volume: 6
  start-page: 65
  issue: 1
  year: 2021
  ident: 19744_CR1
  publication-title: NPJ Vaccines
  doi: 10.1038/s41541-021-00322-7
  contributor:
    fullname: D van de Berg
– volume: 398
  start-page: 137
  issue: 1
  year: 2010
  ident: 19744_CR9
  publication-title: Anal. Bioanal. Chem.
  doi: 10.1007/s00216-010-3781-x
  contributor:
    fullname: AS Rathore
– volume: 27
  start-page: 796
  issue: 5
  year: 2010
  ident: 19744_CR12
  publication-title: Pharm. Res.
  doi: 10.1007/s11095-010-0073-2
  contributor:
    fullname: V Filipe
– volume: 53
  start-page: 107
  issue: 2
  year: 2007
  ident: 19744_CR24
  publication-title: Bull. Osaka Med. Coll.
  contributor:
    fullname: E Daikoku
– volume: 21
  start-page: 204
  issue: 2
  year: 2011
  ident: 19744_CR31
  publication-title: J. Microbiol. Biotechnol.
  doi: 10.4014/jmb.1004.04032
  contributor:
    fullname: I Knabben
– volume: 9
  start-page: 265
  issue: 1
  year: 2012
  ident: 19744_CR13
  publication-title: Virol. J.
  doi: 10.1186/1743-422X-9-265
  contributor:
    fullname: P Kramberger
– volume: 35
  start-page: e2782
  issue: 3
  year: 2019
  ident: 19744_CR23
  publication-title: Biotechnol Prog
  doi: 10.1002/btpr.2782
  contributor:
    fullname: B Moore
– volume: 211
  start-page: 87
  year: 2015
  ident: 19744_CR3
  publication-title: J. Biotechnol.
  doi: 10.1016/j.jbiotec.2015.07.001
  contributor:
    fullname: M Largoni
SSID ssj0000529419
Score 2.4473817
Snippet In the development of end-to-end large-scale live virus vaccine (LVV) manufacturing, process analytical technology (PAT) tools enable timely monitoring of...
Abstract In the development of end-to-end large-scale live virus vaccine (LVV) manufacturing, process analytical technology (PAT) tools enable timely...
Abstract In the development of end-to-end large-scale live virus vaccine (LVV) manufacturing, process analytical technology (PAT) tools enable timely...
SourceID doaj
pubmedcentral
proquest
crossref
springer
SourceType Open Website
Open Access Repository
Aggregation Database
Publisher
StartPage 15494
SubjectTerms 631/1647/2204
631/1647/245
631/1647/328
Acids
Bioreactors
Capacitance
Cell culture
Cell density
Flow cytometry
Genetic engineering
Glycoproteins
Humanities and Social Sciences
Infections
Manufacturing
Measles
Microscopy
Monitoring
multidisciplinary
Nanoparticles
Nucleic acids
Process controls
Proteins
Real time
Science
Science (multidisciplinary)
Vaccines
Vectors (Biology)
Viral infections
Viruses
SummonAdditionalLinks – databaseName: Directory of Open Access Journals
  dbid: DOA
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1LS8QwEA4iCF7EJ9YXEbxpMe0mfRxVFBH0pOAtTJsUF7RdtruL_ntnkq5uBfHitXk1M5Pmm07mC2MnxLCS2cSGQhigMKMKoTIyzA2B1YEQhdP0_UNy-yTvntXzwlVfdCbM0wN7wZ1jP0ICmopRIAur8iqLKwloiKUykfXQSOQLzpRn9Y5zHLjLkhGD7LzFnYqyydD3ihBDy_C9txM5wv4eyvx5RvJHoNTtPzfrbK0DjvzCv_AGW7L1JlvxV0l-bDGzcPqHNxUf-QQADkQ64v5X80nTvLYcQSofw2ho-JtbzjQaNXjFzx6fDcfTls-gpHB7y4c1f4N6SskPLptxmz3dXD9e3YbdDQphqaJ0EkJmilIoSDJly0oluaE4okkBQQIUKZEJplWicFc3tlIFYg-D7gM2iLBQFHaww5brpra7jCMwklaUMsqyUpZpAij9HOG5sCaGJIaAnc6lqUeeKEO7APcg0172GmWvnez1e8AuSeBfNYnk2j1A1etO9fov1QfsYK4u3a28VsdpJHFiSRwH7PirGNcMBUKgts3U1SHaP5WrgKU9NfdeqF9SD18c-3YuU_TZsPezuUF8D_77hPf-Y8L7bDUmA6YbLNQBW56Mp_YQMdGkOHLm_wn_bwrR
  priority: 102
  providerName: Directory of Open Access Journals
– databaseName: AUTh Library subscriptions: ProQuest Central
  dbid: BENPR
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV3_S9wwFH9sJ8J-GU4du01HhP02i2kvadqfRIcig8kYE_wtpEm6HWh7u96J--_3Xpo7V0F_bZomfd_ySV7eewCfKMNK4XOfcO4MuRllYmonktIRWJ1wXgVOf7vML67E12t5HQ_cunitcmUTg6F2raUz8qNMpUIhNs-y49mfhKpGkXc1ltB4CRsZ7hT4CDZOzy6__1ifspAfCycQo2X4pDjqcMWiqDLcg6WIpUVyP1iRQuL-Adp8fFfykcM0rEPnW_A6Akh20nP8DbzwzTZs9iUl_-6A--8WEGtrNusDAZih5CPh3Jot2vamYwhW2dzMpo7dBrWm0ajDDZo_djedLzt2Zyy53Ts2bditaZYUBBGiGnfh6vzs55eLJFZSSKxM1SIxhasslyYvpLe1zEtH_kSnDIIFUylKKqjqXOLq7nwtK8QgDrcR2CHFRl75yVsYNW3j3wFDgCQ8tyItCiusyo10aYkwnXuXmTwzY_i8oqae9QkzdHB0Twrd014j7XWgvb4fwykRfP0mJbsOD9r5Lx11R6MocWHQWjhpROVlWRdZLQzaIouDexxyb8UuHTWw0w_yMoaDdTPqDjlETOPbZXiH0v_JUo5BDdg8mNCwpZn-Dlm4S6Fw74ZfP1wJxMPgT__w--fn-gFeZSSaVKNC7sFoMV_6fUQ9i-pjFO1_oW0C5w
  priority: 102
  providerName: ProQuest
– databaseName: Scholars Portal Journals: Open Access(OpenAccess)
  dbid: M48
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1NT9wwELUQqFIvCCgVS6EyUm8l4HjtfBwQogiEkNpTV-JmTWKnrLQk22QXwb9nxkkoQVTiGsexPR7bbzKeN4x9I4aVxEUuEMICuRl1AIVVQWoJrI6FyPxM__wVXU3U9Y2-WWF9uqNOgM2bph3lk5rUs6OHv4-nuOBP2pDx5LjBQ4gCxdCsChEeqwAx5ZpUaKnTVb4O7rdc3zLF7nSxM29XHZxPnsZ_gD1f35x85T71p9LlBlvv4CQ_a-d_k624cot9aBNMPn5i9sWdIF4VfN6GBXAgKhL_F5svqmrWcISuvIb51PI7v8ipNaoww82Q30_rZcPvIScnfMOnJb-DckkhET7GcZtNLi9-n18FXV6FINdhvAggsVkuNESJdnmho9SSd9HGgNABspgoBuMi0njWW1foDBGJRaMCK4RYKDI3_sxWy6p0O4wjXFJO5CpMklzlcQTahimCduGshEjCiH3vpWnmLX2G8W7vcWJa2RuUvfGyNw8j9oME_vwmUV_7B1X9x3QryaBiCQW4d1gNKnM6LRJZKMCdKcfGHTa510-X6dXJyDhUOLBIyhE7eC7GlUTuEShdtfTvEBmgTvWIxYNpHnRoWFJObz0nd6pitOTw64e9Qvxr_P8D3n1HZ76wj5L0k9JW6D22uqiXbh-B0CL76rX7CV82Bws
  priority: 102
  providerName: Scholars Portal
– databaseName: SpringerOpen
  dbid: C6C
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV1RT9swELZQERIvCDYQZWzypL1BhJPajvPIKhCatD0NiTfrEjuiUptUTVvBv9-dk3akYg97je1ccmf7Pvt8nxn7RgwrxmsfCeGAwowqgtLJKHMEVkdC5MHSP3_ph0f540k9dTQ5lAvTi9-PzE2DDoaSwHDJFCP0lRHixX30wYaOb431eLufQhErFNXlxbzftOd7AkV_D1funorcCY0Gj3N_zI46qMhvW9uesD1ffWAH7eWRrx-Ze3Peh9cln7dH_jkQzUjYoebLup42HGEpX8B84vgsDGCSRg2mONHx9WSxavgaCgqwN3xS8RlUK0p3CPmLp-zx_u73-CHq7kyIChWnywiMywuhQBvli1LpzFHk0KWAsADylOgD01Ir9OPOlypHtOFwwYANYiwUuR-dsUFVV_6ccYRC0otCxsYUskg1KBdnCMiFdwnoBIbsaqNNO2-pMWwIaY-MbXVvUfc26N6-DNl3Uvi2JtFahwdobduNEoudRkjAecEpkLlXWWmSUgLOOgUK9yjycmMu2421xiZpLPHHdJIM2ddtMY4SCn1A5etVqENEfypTQ5b2zNz7oH5JNXkOfNuZTHGVhm-_3nSIv8L__cMX_1f9EztMqKvS7RTqkg2Wi5X_jHhnmX8JHf0PoA36-A
  priority: 102
  providerName: Springer Nature
Title Development of process analytical tools for rapid monitoring of live virus vaccines in manufacturing
URI https://link.springer.com/article/10.1038/s41598-022-19744-x
https://www.proquest.com/docview/2714796622
https://search.proquest.com/docview/2715443595
https://pubmed.ncbi.nlm.nih.gov/PMC9476422
https://doaj.org/article/e6e04a053d5a4be59f82f4a832c5d1ea
Volume 12
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3da9swED_ajsFexj6Z1y5osLfNjWxL_nhcQ0sZpJSxQt6ELMlbILFDnJTtv--dbHd1YS97MdiyOdl3J_3ku_sJ4BMxrOQudSHnVlOYUYa6siIsLIHVhPPSa3p-lV7eiG8LuTgAOdTC-KR9Uy5P69X6tF7-8rmVm7WZDnli0-v5rBAZwuZ4egiHaKAPlugdoXdcoMy-QIYn-bTFSYoKyXDZFSF8FiGRTyfEMy5FMpqPPG3_CGs-zpR8FC71s9DFC3jew0f2tevmSzhw9St42m0o-ec12Ac5QKyp2KYrA2CaqEf8X2u2a5pVyxCqsq3eLC1be6cmafTACgc_drvc7lt2qw0F3Vu2rNla13sqgfA1jW_g5uL8x-wy7PdRCI2Msl2oc1saLnWaS2cqmRaWook20wgVdJkRpWBWpRLndusqWSICsbiIwAcibOSlS97CUd3U7h0whEfCcSOiPDfCZKmWNioQpHNnY53GOoDPw9dUm44uQ_kwd5KrTg0K1aC8GtTvAM7og9_fSVTX_kKz_al6hSs0JC40jhVWalE6WVR5XAmNI5FB4Q5FngzqUr3_tSrOIoEvlsZxAB_vm9FzKByia9fs_T1E_icLGUA2UvOoQ-MWNEnPwd2bYABfBoP4K_zfL_z-vwUdw7OYDJg2r5AncLTb7t0HhEO7coJOsMgm8OTs_Or6O57N0tnE_1rA41zkE-8ed07nD6g
link.rule.ids 230,315,730,783,787,867,888,2109,12068,21400,24330,27936,27937,31731,31732,33756,33757,41132,42201,43322,43817,51588,53804,53806,74073,74630
linkProvider National Library of Medicine
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV3fT9swELYYaNpeEGObKD82T-Jti3BSO06eJpiGug14Aqlv1sV2oBIkXdMi-O9356RlQdpe4ySXnM_nzz7fd4wdEsNK5lMfCeGAwowqgtLJKHcEVodCFKGnzy_S0ZX8OVbjbsOt6Y5VLn1icNSutrRHfpToWGrE5knydfo7oqpRFF3tSmi8YBvEw0UVDPRYr_ZYKIqF4rtcGTHMjhqcryinDFdgMSJpGT305qNA29_Dms9PSj4Ll4ZZ6HSLbXbwkR-3_f2Grflqm71sC0o-vmXurzNAvC75tE0D4EDUI2HXms_r-rbhCFX5DKYTx-_CoCZp9MAtOj9-P5ktGn4PloLuDZ9U_A6qBaVAhJzGd-zq9Pvlt1HU1VGIrIr1PILMFVYoSDPlbanS3FE00WlAqACFJkpBXaYK53bnS1UgAnG4iMAHYmwUhR--Z-tVXfkdxhEeSS-sjLPMSqtTUC7OEaQL7xJIExiwz0ttmmlLl2FCmHuYmVb3BnVvgu7Nw4CdkMJXdxLVdbhQz65NN3IMGpKQgL7CKZCFV3mZJaUE9EQWhXsUub_sLtONv8Y8WcuAfVo148ihcAhUvl6Ee4j8T-VqwHSvm3sf1G-pJjeBgzuXGldu-PYvS4N4Ev7vH979_7d-ZK9Gl-dn5uzHxa899johM6VqFWqfrc9nC3-A-GdefAhG_geczARy
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV3db9MwED9BJxAviE_RbYCReIOoTmLHyRNisGp8VRNi0t4sJ3ZGpS0pTTuN_547x-3IJHiN49i5O59_9n0BvKYMK7nLXMS5NWRmlJGprYgKS2A15bz0nP42y45OxOdTeRr8n7rgVrnRiV5R27aiO_JJomKhEJsnyaQObhHHH6fvFr8iqiBFltZQTuM27CiRpXwEOweHs-Pv2xsXsmnhZELkDE_zSYe7F0WY4XksRlwtoqvB7uST-A-Q502_yRvGU78nTR_A_QAm2fue-w_hlmsewZ2-vOTvx2D_8ghibc0WfVAAM5SIxN9hs1XbnncMgStbmsXcsgu_xGk06nCOqpBdzpfrjl2aikzwHZs37MI0awqI8BGOT-Bkevjjw1EUqipElYzVKjK5LSsuTZZLV9UyKyzZFq0yCBxMqSjBoKoziTu9dbUsEY9YPFJghxgbeenSpzBq2sY9A4ZgSTheiTjPK1GpzEgbFwjZubOJyRIzhjcbaupFnzxDe6N3muue9hpprz3t9dUYDojg2zcp8bV_0C7PdFhHGsWKC4Oaw0ojSieLOk9qYVAvVTi4wyH3N-zSYTV2-lp2xvBq24zriIwjpnHt2r9DqQBlIcegBmweTGjY0sx_-ozchVB4jsOvv90IxPXg__7h3f_P9SXcRQnXXz_NvuzBvYSklEpXyH0YrZZr9xzB0Kp8EaT8DzBZCg8
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Development+of+process+analytical+tools+for+rapid+monitoring+of+live+virus+vaccines+in+manufacturing&rft.jtitle=Scientific+reports&rft.au=Yi%2C+Sijia&rft.au=McCracken%2C+Reilly&rft.au=Davide%2C+Joseph&rft.au=Salovich%2C+Daniel+Ryan&rft.date=2022-09-15&rft.eissn=2045-2322&rft.volume=12&rft.issue=1&rft.spage=15494&rft.epage=15494&rft_id=info:doi/10.1038%2Fs41598-022-19744-x&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2045-2322&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2045-2322&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2045-2322&client=summon