Solti Katalin, Timári Sarolta, Faludi Tamás, Iliás Attila, Hegedüs Rózsa, Pataj Zoltán, Háda Viktor
Biotechnology Process Development & Analytics, Biotechnology Business Unit, Gedeon Richter Plc., Gyömrői út 19-21., 1103, Budapest, Hungary.
BioDrugs. 2025 Sep;39(5):675-696. doi: 10.1007/s40259-025-00734-0. Epub 2025 Aug 1.
BACKGROUND AND OBJECTIVE: Tocilizumab is a recombinant, humanised monoclonal antibody of the immunoglobulin G1 (IgG1) subclass, which specifically targets the interleukin-6 receptor (IL-6R). The RGB-19 product was developed as a biosimilar to the reference medicinal product RoActemra (authorised for use in the European Union [EU]). The current study focuses on the demonstration of structural, physico-chemical and functional similarity between RGB-19 (intravenous [IV] and subcutaneous [SC] presentations) and EU-sourced RoActemra (IV and SC presentations). METHODS: The RGB-19 biosimilar tocilizumab product was comprehensively tested using an extensive state-of-the-art analytical and functional panel of 44 methods to demonstrate similarity to the EU-sourced RoActemra. Biosimilarity was rigorously evaluated through an extensive array of orthogonal physico-chemical and functional assays, supplemented by a detailed comparative characterisation of the primary and higher order structures of the therapeutic proteins. RESULTS: Extensive structural analyses confirmed that the primary and higher order structures of tocilizumab proteins in RGB-19 IV and SC drug products are identical or exhibit a high degree of similarity to those of the RoActemra reference products. The impurity profiles of RGB-19 and RoActemra products were found to be highly comparable, as demonstrated by a series of physico-chemical techniques. A high level of similarity was shown for the most critical (soluble IL-6R binding and cell-based anti-proliferation assay) and for all other bioassay attributes. Based on the statistical evaluation, negligible differences could be detected for sialylation, glycation, fragments and charge variants, which do not affect the functional properties. CONCLUSION: Based on the similarity study, RGB-19 and RoActemra can be considered highly similar drug products. The minor differences found for some physico-chemical attributes do not affect the biological potency, binding and other critical attributes, and are therefore not considered clinically meaningful.
背景与目的：托珠单抗是一种重组人源化免疫球蛋白G1（IgG1）亚类单克隆抗体，特异性靶向白细胞介素-6受体（IL-6R）。RGB-19产品作为参照药品RoActemra（已获欧盟批准使用）的生物类似药而研发。本研究聚焦于证明RGB-19（静脉注射[IV]和皮下注射[SC]剂型）与欧盟来源的RoActemra（IV和SC剂型）在结构、物理化学和功能上的相似性。 方法：使用一套涵盖44种方法的先进分析和功能检测方法，对RGB-19生物类似药托珠单抗产品进行全面测试，以证明其与欧盟来源的RoActemra相似。通过一系列正交物理化学和功能检测对生物相似性进行严格评估，并辅以治疗性蛋白质一级和高级结构的详细比较表征。 结果：广泛的结构分析证实，RGB-19 IV和SC药品中托珠单抗蛋白的一级和高级结构与RoActemra参照产品相同或高度相似。一系列物理化学技术表明，RGB-19和RoActemra产品的杂质谱高度可比。在最关键的（可溶性IL-6R结合和基于细胞的抗增殖检测）以及所有其他生物检测属性方面都显示出高度相似性。基于统计评估，在唾液酸化、糖基化、片段和电荷变体方面检测到的差异可忽略不计，这些差异不影响功能特性。 结论：基于相似性研究，RGB-19和RoActemra可被视为高度相似的药品。在一些物理化学属性上发现的微小差异不影响生物学效力、结合及其他关键属性，因此不被认为具有临床意义。
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