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 - Special Issue: Celebrating Professor Ziad El Rassi's 70th Birthday and His 25 Years of Dedication to Electrophoresis.
PY - 2019/9
Y1 - 2019/9
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
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U2 - 10.1002/elps.201900068
DO - 10.1002/elps.201900068
M3 - Article
C2 - 30951206
SN - 0173-0835
VL - 40
SP - 2277
EP - 2284
JO - Electrophoresis
JF - Electrophoresis
IS - 18-19
ER -