Workflow for criticality assessment applied in biopharmaceutical process validation stage 1

Autoren Thomas Zahel
Lukas Marschall
Sandra Abad
Elena Vasilieva
Daniel Maurer
Eric M. Mueller
Patrick Murphy
Thomas Natschläger
Céline Brocard
Daniela Reinisch
Patrick Sagmeister
Christoph Herwig
Titel Workflow for criticality assessment applied in biopharmaceutical process validation stage 1
Typ Artikel
Journal bioengineering
Nummer 4
Band 4
DOI 10.3390/bioengineering4040085
Monat October
Jahr 2017
SCCH ID# 17073

Identification of critical process parameters that impact product quality is a central task during regulatory requested process validation. Commonly, this is done via design of experiments and identification of parameters significantly impacting product quality (rejection of the null hypothesis that the effect equals 0). However, parameters which show a large uncertainty and might result in an undesirable product quality limit critical to the product, may be missed. This might occur during the evaluation of experiments since residual/un-modelled variance in the experiments is larger than expected a priori. Estimation of such a risk is the task of the presented novel retrospective power analysis permutation test. This is evaluated using a data set for two unit operations established during characterization of a biopharmaceutical process in industry. The results show that, for one unit operation, the observed variance in the experiments is much larger than expected a priori, resulting in low power levels for all non-significant parameters. Moreover, we present a workflow of how to mitigate the risk associated with overlooked parameter effects. This enables a statistically sound identification of critical process parameters. The developed workflow will substantially support industry in delivering constant product quality, reduce process variance and increase patient safety.