Implementation of at-line capillary zone electrophoresis for fast and reliable determination of adenovirus concentrations in vaccine manufacturing

Ewoud van Tricht, Lars Geurink, Francisca Galindo Garre, Martijn Schenning, Harold Backus, Marta Germano, Govert W. Somsen, Cari E. Sänger – van de Griend

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

A CZE method was validated and implemented for fast and accurate in-process determination of adenovirus concentrations of downstream process samples obtained during manufacturing of adenovirus vector-based vaccines. An analytical-quality-by-design approach was embraced for method development, method implementation, and method maintenance. CZE provided separation of adenovirus particles from sample matrix components, such as cell debris, residual DNA and proteins. The intermediate precision of the virus particle concentration was 6.9% RSD and the relative bias was 2.3%. In comparison, the CZE method is intended to replace a quantitative polymerase chain reaction method which requires three replicates in three analytical runs to achieve an intermediate precision of 8.1% RSD. Given that, in addition, the time from sampling till reporting results of the CZE method was less than 2 h, whereas quantitative polymerase chain reaction requires 3 days, it follows that the CZE method enables faster processing times in downstream processing.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalElectrophoresis
DOIs
Publication statusE-pub ahead of print - 5 Apr 2019

Fingerprint

Polymerase chain reaction
Capillary Electrophoresis
Electrophoresis
Adenoviridae
Vaccines
Processing
Viruses
Debris
Sampling
DNA
Proteins
Polymerase Chain Reaction
Virion
Maintenance

Bibliographical note

This article is protected by copyright. All rights reserved.

Keywords

  • Analytical quality by design
  • At-line IPC testing
  • Capillary zone electrophoresis lifecycle management
  • Virus quantification

Cite this

@article{644bcc07e1724938b3b713528340af07,
title = "Implementation of at-line capillary zone electrophoresis for fast and reliable determination of adenovirus concentrations in vaccine manufacturing",
abstract = "A CZE method was validated and implemented for fast and accurate in-process determination of adenovirus concentrations of downstream process samples obtained during manufacturing of adenovirus vector-based vaccines. An analytical-quality-by-design approach was embraced for method development, method implementation, and method maintenance. CZE provided separation of adenovirus particles from sample matrix components, such as cell debris, residual DNA and proteins. The intermediate precision of the virus particle concentration was 6.9{\%} RSD and the relative bias was 2.3{\%}. In comparison, the CZE method is intended to replace a quantitative polymerase chain reaction method which requires three replicates in three analytical runs to achieve an intermediate precision of 8.1{\%} RSD. Given that, in addition, the time from sampling till reporting results of the CZE method was less than 2 h, whereas quantitative polymerase chain reaction requires 3 days, it follows that the CZE method enables faster processing times in downstream processing.",
keywords = "Analytical quality by design, At-line IPC testing, Capillary zone electrophoresis lifecycle management, Virus quantification",
author = "{van Tricht}, Ewoud and Lars Geurink and {Galindo Garre}, Francisca and Martijn Schenning and Harold Backus and Marta Germano and Somsen, {Govert W.} and {S{\"a}nger – van de Griend}, {Cari E.}",
note = "This article is protected by copyright. All rights reserved.",
year = "2019",
month = "4",
day = "5",
doi = "10.1002/elps.201900068",
language = "English",
pages = "1--8",
journal = "Electrophoresis",
issn = "0173-0835",
publisher = "Wiley-VCH Verlag",

}

Implementation of at-line capillary zone electrophoresis for fast and reliable determination of adenovirus concentrations in vaccine manufacturing. / van Tricht, Ewoud; Geurink, Lars; Galindo Garre, Francisca; Schenning, Martijn; Backus, Harold; Germano, Marta; Somsen, Govert W.; Sänger – van de Griend, Cari E.

In: Electrophoresis, 05.04.2019, p. 1-8.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Implementation of at-line capillary zone electrophoresis for fast and reliable determination of adenovirus concentrations in vaccine manufacturing

AU - van Tricht, Ewoud

AU - Geurink, Lars

AU - Galindo Garre, Francisca

AU - Schenning, Martijn

AU - Backus, Harold

AU - Germano, Marta

AU - Somsen, Govert W.

AU - Sänger – van de Griend, Cari E.

N1 - This article is protected by copyright. All rights reserved.

PY - 2019/4/5

Y1 - 2019/4/5

N2 - A CZE method was validated and implemented for fast and accurate in-process determination of adenovirus concentrations of downstream process samples obtained during manufacturing of adenovirus vector-based vaccines. An analytical-quality-by-design approach was embraced for method development, method implementation, and method maintenance. CZE provided separation of adenovirus particles from sample matrix components, such as cell debris, residual DNA and proteins. The intermediate precision of the virus particle concentration was 6.9% RSD and the relative bias was 2.3%. In comparison, the CZE method is intended to replace a quantitative polymerase chain reaction method which requires three replicates in three analytical runs to achieve an intermediate precision of 8.1% RSD. Given that, in addition, the time from sampling till reporting results of the CZE method was less than 2 h, whereas quantitative polymerase chain reaction requires 3 days, it follows that the CZE method enables faster processing times in downstream processing.

AB - A CZE method was validated and implemented for fast and accurate in-process determination of adenovirus concentrations of downstream process samples obtained during manufacturing of adenovirus vector-based vaccines. An analytical-quality-by-design approach was embraced for method development, method implementation, and method maintenance. CZE provided separation of adenovirus particles from sample matrix components, such as cell debris, residual DNA and proteins. The intermediate precision of the virus particle concentration was 6.9% RSD and the relative bias was 2.3%. In comparison, the CZE method is intended to replace a quantitative polymerase chain reaction method which requires three replicates in three analytical runs to achieve an intermediate precision of 8.1% RSD. Given that, in addition, the time from sampling till reporting results of the CZE method was less than 2 h, whereas quantitative polymerase chain reaction requires 3 days, it follows that the CZE method enables faster processing times in downstream processing.

KW - Analytical quality by design

KW - At-line IPC testing

KW - Capillary zone electrophoresis lifecycle management

KW - Virus quantification

UR - http://www.scopus.com/inward/record.url?scp=85064480198&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064480198&partnerID=8YFLogxK

U2 - 10.1002/elps.201900068

DO - 10.1002/elps.201900068

M3 - Article

SP - 1

EP - 8

JO - Electrophoresis

JF - Electrophoresis

SN - 0173-0835

ER -