Eine alternative zum tierversuch in der qualitätskontrolle von erythropoietin

Teil 1

authored by: Hanne Zimmermann, Daniel Gerhard, Ludwig A. Hothorn, Theodor Dingermann
Abstract: As an alternative to the current bioassay in normocythaemic mice a physico-chemical method was developed for estimating the biological activity of erythropoietin batches. Capillary electrophoresis was used for quantification of the isoforms and their substructures were further elucidated by N-glycan mapping techniques. The analytical study was performed on a total of 40 batches of Epoetin beta® which were selected to cover adequate range of precisely established potency values. The relations between the biological and chemical parameters were statistically evaluated in order to identify suitable as covariates for prediction of the biological activity. Among several alternatives a prediction model was selected and tested, which is based on the percentages of isoforms per batch and its degree of sialylation. This model is equivalent to the established in vivo bioassay in terms of accuracy but it is far superior in terms of precision. Further advantages emerge from animal welfare as well as from savings of time and effort. The question whether the prediction model already meets the requirements for replacing the bioassay according to the ICH guideline Q6B is discussed.
Organisation(s): Department of Biostatistics
External Organisation(s): Roche Diagnostics GmbH
Goethe University Frankfurt
Type: Survey paper
Journal: Pharmazeutische Industrie
Volume: 72
Pages: 708-712
No. of pages: 5
ISSN: 0031-711X
Publication date: 2010
Publication status: Published
Peer reviewed: Yes
ASJC Scopus subject areas: Pharmaceutical Science

BibTeX

@article{cc2d5dcce7814a0e8580234dafc961bd,
title = "Eine alternative zum tierversuch in der qualit{\"a}tskontrolle von erythropoietin: Teil 1",
abstract = "As an alternative to the current bioassay in normocythaemic mice a physico-chemical method was developed for estimating the biological activity of erythropoietin batches. Capillary electrophoresis was used for quantification of the isoforms and their substructures were further elucidated by N-glycan mapping techniques. The analytical study was performed on a total of 40 batches of Epoetin beta{\textregistered} which were selected to cover adequate range of precisely established potency values. The relations between the biological and chemical parameters were statistically evaluated in order to identify suitable as covariates for prediction of the biological activity. Among several alternatives a prediction model was selected and tested, which is based on the percentages of isoforms per batch and its degree of sialylation. This model is equivalent to the established in vivo bioassay in terms of accuracy but it is far superior in terms of precision. Further advantages emerge from animal welfare as well as from savings of time and effort. The question whether the prediction model already meets the requirements for replacing the bioassay according to the ICH guideline Q6B is discussed.",
keywords = "Biologische aktivit{\"a}t, Erythropoietin, Glykosylierung, Kapillarelektrophorese, Pr{\"a}diktionsmodell, Tierversuch",
author = "Hanne Zimmermann and Daniel Gerhard and Hothorn, {Ludwig A.} and Theodor Dingermann",
year = "2010",
language = "Deutsch",
volume = "72",
pages = "708--712",
journal = "Pharmazeutische Industrie",
issn = "0031-711X",
publisher = "Editio Cantor Verlag GmbH",
number = "4",
}