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Understanding the contribution of operator measurement variability within flow cytometry data analysis for quality control of cell and gene therapy manufacturing

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journal contribution
posted on 28.08.2019, 15:38 authored by Becky Grant, Karen CoopmanKaren Coopman, Nick Medcalf, Sandro Silva-Gomes, Jonathan Campbell, Bo Kara, Julian Braybrook, Jon PetzingJon Petzing
Flow Cytometry is a measurement technique used in Quality Control and in-process measurements of biomanufactured Cell and Gene Therapy products. However, it contains a number of sources of measurement variation at; sample preparation, instrument setup, analysis, and post-analytical data analysis stages. The latter sees variation introduced from operator subjectivity, which is investigated here to understand what effects the interpretation of diagrammatical protocols have on inter-operator analysis. 36 operators from different sites were given a series of histograms to analyse, gating a shifting peak. This was repeated with diagrammatical protocols to apply gates which reduced inter-operator variation by up to 92%. Various control limits include and exclude different results and when adjusted with a log transform differences in outlier discrimination have been found. This research supports the use of Flow Cytometry diagrammatical protocols to reduce the contribution of inter-operator variation and measurement uncertainty associated within Cell and Gene Therapy manufacturing scenarios.

Funding

Loughborough University Doctoral College

EPSRC/MRC Doctoral Training Centre for Regenerative Medicine at Loughborough University (EP/L105072/1)

GlaxoSmithKline

LGC

History

School

  • Mechanical, Electrical and Manufacturing Engineering
  • Aeronautical, Automotive, Chemical and Materials Engineering

Department

  • Chemical Engineering

Published in

Measurement

Volume

150

Publisher

Elsevier

Version

AM (Accepted Manuscript)

Rights holder

© Elsevier Ltd.

Publisher statement

This paper was accepted for publication in the journal Measurement and the definitive published version is available at https://doi.org/10.1016/j.measurement.2019.106998.

Acceptance date

28/08/2019

Publication date

2019-08-30

Copyright date

2019

ISSN

0263-2241

Language

en

Depositor

Dr Jon Petzing

Article number

106998