How bio-questionable are the different recombinant human erythropoietin copy products in Thailand?

Autor: Halim LA; Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands., Brinks V, Jiskoot W, Romeijn S, Praditpornsilpa K, Assawamakin A, Schellekens H
Jazyk: angličtina
Zdroj: Pharmaceutical research [Pharm Res] 2014 May; Vol. 31 (5), pp. 1210-8. Date of Electronic Publication: 2013 Nov 21.
DOI: 10.1007/s11095-013-1243-9
Abstrakt: Purpose: The high prevalence of pure red cell aplasia in Thailand has been associated with the sharp increase in number of recombinant human erythropoietin (rhEPO) copy products, based on a classical generic regulatory pathway, which have entered the market. This study aims to assess the quality of rhEPO copy products being used in Thailand.
Methods: Twelve rhEPO copy products were purchased from pharmacies in Thailand, shipped under controlled cold chain conditions to the Netherlands and characterized using (1) high performance size-exclusion chromatography, (2) asymmetrical flow field-flow fractionation, (3) sodium dodecyl sulfate polyacrylamide gel electrophoresis in combination with (4) Western blotting and additionally tested for (5) host cell protein impurities as well as (6) endotoxin contamination.
Results: Some of the tested rhEPO copy products showed high aggregate levels and contained a substantial amount of protein fragments. Also, one of rhEPO copy products had a high endotoxin level, exceeding the FDA limit.
Conclusions: Our observations show that some of the tested copy products on the Thai market differ significantly from the originator rhEPO product, Epogen®. This comparison study supports a link between the quality attributes of copy rhEPO products and their immunogenicity.
Databáze: MEDLINE
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