Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, Room 3.76, 3584, CG, Utrecht, The Netherlands.
Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav), Av. IPN 2508, Col. San Pedro Zacatenco, C.P, 07360, Ciudad de México, Mexico.
Pharm Res. 2018 Oct 2;35(11):226. doi: 10.1007/s11095-018-2491-5.
Filgrastim, a recombinant human granulocyte-colony stimulating factor, is widely used to treat congenital and acquired neutropenia. Following patent expiration of the innovator filgrastim product, biosimilar filgrastim products have been approved in the EU and shown to be comparable with the innovator with respect to quality, safety and efficacy. In less regulated markets, copy filgrastim products are available but data about their quality are scarce. In the present study, we provide a head-to-head comparative study on the quality of biosimilar and copy filgrastim products.
Innovator filgrastim product, Neupogen®, two EU-licensed biosimilars, Zarzio® and Tevagrastim®, and two copy filgrastim products, Biocilin® and PDgrastim®, were subjected to peptide mapping, circular dichroism spectroscopy, fluorescence spectroscopy, sodium dodecyl sulfate polyacrylamide gel electrophoresis, high performance size-exclusion chromatography, reversed-phase ultra-performance liquid chromatography, endotoxin test, flow imaging microscopy and in vitro potency assay.
Zarzio® and Tevagrastim® have comparable quality to Neupogen®, while Biocilin® showed a significantly lower and PDgrastim® a higher specific activity. Moreover, PDgrastim® showed a higher level of impurities and a lower thermo stability than the other products.
Except for the deviating specific activities of the two copy filgrastim products, we found no substantial differences in product quality between the filgrastim products studied.
非格司亭（一种重组人粒细胞集落刺激因子）被广泛用于治疗先天性和获得性中性粒细胞减少症。在原研非格司亭产品专利到期后，生物类似药非格司亭产品已在欧盟获得批准，其在质量、安全性和疗效方面与原研产品相当。在监管较少的市场中，也有仿制药非格司亭产品，但关于其质量的数据却很少。在本研究中，我们对生物类似药和仿制药非格司亭产品的质量进行了头对头的比较研究。
对原研非格司亭产品 Neupogen®、两个获得欧盟许可的生物类似药 Zarzio®和 Tevagrastim®，以及两个仿制药非格司亭产品 Biocilin®和 PDgrastim®进行肽图分析、圆二色光谱分析、荧光光谱分析、十二烷基硫酸钠聚丙烯酰胺凝胶电泳、高效尺寸排阻色谱、反相超高效液相色谱、内毒素检测、流成像显微镜和体外效价测定。
Zarzio®和 Tevagrastim®与 Neupogen®具有相当的质量，而 Biocilin®的比活性显著较低，PDgrastim®的比活性则较高。此外，PDgrastim®比其他产品具有更高的杂质水平和更低的热稳定性。
除了两种仿制药非格司亭产品的比活性存在差异外，我们在研究的非格司亭产品之间没有发现产品质量的实质性差异。
