Quality Evaluation Team, Samsung Bioepis Co., Ltd, 107, Cheomdan-daero, Yeonsu-gu, Incheon, 21987, Republic of Korea.
BioDrugs. 2019 Aug;33(4):411-422. doi: 10.1007/s40259-019-00362-5.
SB3 has been developed as a trastuzumab biosimilar, a therapeutic monoclonal antibody targeted to human epidermal growth factor receptor 2 (HER2), and approved by the European Commission and United States (US) Food and Drug Administration (FDA). During the developmental period of a biosimilar, setting an appropriate quality target is critical for assessing the similarity of the biosimilar product to the reference product. A stepwise approach should be taken to assessing similarity, beginning with extensive characterization of the reference product to establish the quality target.
In this study, we evaluated the similarity of SB3 to the reference product and the impact of changes in the biological profile of the reference product on similarity assessment.
Analytical similarity was assessed with defined test procedures in terms of critical quality attributes (CQAs) that could affect efficacy, potency, and safety, as well as for the non-CQAs that are related to process consistency. The quality target was established using up to 154 lots of European Union (EU)- and US-sourced Herceptin (reference product), analyzed during the developmental period of SB3.
Trends of the EU- and US-sourced reference product showed that the biological profile exhibited two marked changes for Fc-related attributes, and then recovered to pre-change quality level. Since the similarity range set by pre-change lots was considered most relevant, the changed lots were excluded from establishing the similarity range, which resulted in tightened acceptance criteria. As shown in the results of similarity assessment using the stringent quality target ranges, SB3 exhibits highly similar functional activities compared to the reference product in terms of both CQAs and non-CQAs.
SB3 has been developed as a trastuzumab biosimilar approved in the EU and USA, and its manufacturing process is deemed to be robust and well-controlled within stringent quality target ranges.
SB3 是一种曲妥珠单抗生物类似药，是一种针对人表皮生长因子受体 2（HER2）的治疗性单克隆抗体，已获得欧洲委员会和美国食品药品监督管理局（FDA）批准。在生物类似药的开发过程中，为评估生物类似药产品与参比产品的相似性，设定适当的质量目标至关重要。应采取逐步方法评估相似性，首先对参比产品进行广泛的特征描述，以确定质量目标。
本研究旨在评估 SB3 与参比产品的相似性，以及参比产品生物学特征变化对相似性评估的影响。
通过定义的测试程序，从可能影响疗效、效价和安全性的关键质量属性（CQA）以及与工艺一致性相关的非 CQA 方面评估分析相似性。质量目标使用多达 154 批欧盟（EU）和美国来源的赫赛汀（参比产品）建立，这些批次在 SB3 的开发期间进行了分析。
EU 和美国来源的参比产品的趋势表明，Fc 相关属性的生物学特征发生了两次明显变化，然后恢复到变化前的质量水平。由于考虑到变化前批次的相似性范围最相关，因此将变化批次排除在相似性范围的建立之外，这导致了更严格的验收标准。正如使用严格的质量目标范围进行相似性评估的结果所示，SB3 在 CQA 和非 CQA 方面均表现出与参比产品高度相似的功能活性。
SB3 已被开发为一种曲妥珠单抗生物类似药，在欧盟和美国获得批准，其制造工艺被认为在严格的质量目标范围内是稳健且得到良好控制的。
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