Фармацевтика Аналитика Акта

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Ibio Number Assay and Erythropoietin Bioactivity: Comparison of the Calculated and the Stated Potencies of the Biological Reference Preparations of Erythropoietin

Hermentin P

The potencies of the biological reference preparations of erythropoietin, assigned by the European Pharmacopoeia Commission on the basis of the normocythaemic and polycythaemic mouse bioassay for erythropoietin, have retrospectively been calculated by the author via the Ibio-number assay, a physicochemical assay based on capillary zone electrophoresis data that allows to calculate the potency of erythropoietin medicinal products. The retrospective analysis by the author of the capillary electrophoresis data of three collaborative studies published in 2004, 2007 and 2015 has revealed that the potencies assigned for erythropoietin reference preparations batch 1 and batch 2 (~130.0 IU/μg, each) have been stated ~5 % too low respectively ~10 % too low, whereas the potency stated for erythropoietin reference preparation batch 3 (~141.1 IU/μg) was confirmed (difference to the stated potency = -1.2%) and therefore free of doubts. Thus, erythropoietin medicinal products that have been calibrated against erythropoietin reference preparation batch 1 or batch 2 have been subject to the same error which was, however, within the error of the mouse bioassay and therefore not crucial. With respect to erythropoietin concentrated solution batch release according to the European Pharmacopoeia, the very broad criteria for erythropoietin identification via capillary zone electrophoresis (which is based on broad ranges defined for the various erythropoietin isoforms) could be replaced by a single and quite narrow Ibio-number range, which would provide a significant increase in assay precision and accuracy and hence in drug safety. Moreover, the Ibio-number assay could be a candidate physicochemical assay to replace the mouse bioassay in the quality control of erythropoietin batch release.