Assessment of rhEPO in Pharmaceutical Formulations by a Reversed‐Phase Liquid Chromatography Method and Bioassay

How institutional logics hamper innovation: The case of animal testing

“…Potency is the ability of medicines to exert their intended activity (Mire-Sluis, 2001). EPO potency is dependent on correct folding for binding affinity and signal transduction and on glycosylation to decelerate clearing from the body by the liver (Imai et al, 1990;Watson and Yao, 1993;Barth et al, 2007;Ferretto et al, 2009).…”

“…Before EPO received market approval in the 1990s, several studies had already been done to develop animal-free methods to assess EPO potency (entrepreneurial activity). It had taken decades of research to correlate the potency of protein medicines in animals with the results of animal-free methods (knowledge development), and the development of animal-free methods for EPO potency testing showed additional difficulties (Barth et al, 2007). The potency of most protein medicines depends only on binding affinity and signal transduction, whereas for EPO potency there is also a strong, but not fully understood, correlation between glycosylation and potency (Imai et al, 1990;Watson and Yao, 1993;Barth et al, 2007;Ferretto et al, 2009, Industry1, 2011.…”

A pilot study on potency determination of human follicle-stimulating hormone: A comparison between reversed-phase high-performance liquid chromatography method and the in vivo bioassay

“…Efforts have been made to develop tests for potency assessment that avoid the use of animals. There are already in the literature physical-chemical methods showing a good correlation with in vivo assays [12][13][14][15][16][17]. RP-HPLC was proposed as a possible alternative to the normocythaemic mice bioassay for the potency assessment of recombinant human erythropoietin [12].…”

“…There are already in the literature physical-chemical methods showing a good correlation with in vivo assays [12][13][14][15][16][17]. RP-HPLC was proposed as a possible alternative to the normocythaemic mice bioassay for the potency assessment of recombinant human erythropoietin [12]. The in vivo bioactivity of a therapeutic glycoprotein, human follicle-stimulating hormone (hFSH), used in the treatment of human infertility [18][19][20], could be predicted by using quantitative charge-based separation methods like isoelectric focusing and capillary zone electrophoresis.…”

Determinação de potência de diferentes preparações de foliculotrofina, luteotrofina e tireotrofina: comparação entre a quantificação por cromatografia líquida em fase reversa e por bioensaio in vivo

“…A substituição de bioensaios por métodos físico-químicos no caso de glicoproteínas é particularmente difícil, principalmente levando em conta a complexidade destas moléculas e a heterogeneidade da sua glicosilação. RP-HPLC, bem como HPSEC, foram propostos como uma possível alternativa para o bioensaio em camundongos normocitêmicos para a determinação da potência de eritropoietina humana recombinante (rhEPO) (Barth, 2007;Ferreto, 2009;Schutkoski, 2013 (Driebergen, 2003;Bassett, 2005). (Hartree, 1992;Galet, 2004).…”