Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
Pharm Res. 2014 May;31(5):1210-8. doi: 10.1007/s11095-013-1243-9. Epub 2013 Nov 21.
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.
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.
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.
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.
由于经典的通用监管途径，大量重组人红细胞生成素（rhEPO）仿制产品进入市场，导致泰国纯红细胞再生障碍性贫血的发病率很高。本研究旨在评估泰国使用的 rhEPO 仿制产品的质量。
从泰国的药店购买了 12 种 rhEPO 仿制产品，在受控冷链条件下运往荷兰，并使用（1）高效尺寸排阻色谱法、（2）不对称流场流分离、（3）十二烷基硫酸钠聚丙烯酰胺凝胶电泳结合（4）Western blot 进行表征，并进一步测试（5）宿主细胞蛋白杂质和（6）内毒素污染。
一些测试的 rhEPO 仿制产品显示出高聚集体水平，并含有大量的蛋白质片段。此外，一种 rhEPO 仿制产品的内毒素水平很高，超过了 FDA 的限制。
我们的观察结果表明，泰国市场上的一些测试仿制产品与原研 rhEPO 产品 Epogen®有很大的不同。这项比较研究支持了仿制 rhEPO 产品的质量属性与其免疫原性之间的联系。
