Details
| Translated title of the contribution | An alternative to animal experiments in the quality control of erythropoietin |
|---|---|
| Original language | German |
| Pages (from-to) | 708-712 |
| Number of pages | 5 |
| Journal | Pharmazeutische Industrie |
| Volume | 72 |
| Issue number | 4 |
| Publication status | Published - 2010 |
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.
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmaceutical Science
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In: Pharmazeutische Industrie, Vol. 72, No. 4, 2010, p. 708-712.
Research output: Contribution to journal › Survey paper › Research › peer review
}
TY - JOUR
T1 - Eine alternative zum tierversuch in der qualitätskontrolle von erythropoietin
T2 - Teil 1
AU - Zimmermann, Hanne
AU - Gerhard, Daniel
AU - Hothorn, Ludwig A.
AU - Dingermann, Theodor
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - Biologische aktivität
KW - Erythropoietin
KW - Glykosylierung
KW - Kapillarelektrophorese
KW - Prädiktionsmodell
KW - Tierversuch
UR - http://www.scopus.com/inward/record.url?scp=77951771925&partnerID=8YFLogxK
M3 - Survey Paper
AN - SCOPUS:77951771925
VL - 72
SP - 708
EP - 712
JO - Pharmazeutische Industrie
JF - Pharmazeutische Industrie
SN - 0031-711X
IS - 4
ER -