<br>使用先进的分析技术对贝伐珠单抗上市制剂进行比较稳定性研究和聚集体分析,Heliyon

当前位置： X-MOL 学术 › Heliyon › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

使用先进的分析技术对贝伐珠单抗上市制剂进行比较稳定性研究和聚集体分析
Heliyon ( IF 3.4 ) Pub Date : 2023-08-28 , DOI: 10.1016/j.heliyon.2023.e19478
Arpit Arunkumar Bana ₁ , Nithin Sajeev ₂ , Sabyasachi Halder ₂ , Haidar Abbas Masi ₃ , Shikha Patel ₁ , Priti Mehta ₁

Affiliation

贝伐珠单抗（Bvz）是生物仿制药开发中最受欢迎的重组人源化单克隆抗体，因为它在肿瘤学领域作为标准治疗药物的地位突出。治疗性单克隆抗体通常更复杂，不太可能产生复制品。因此，监管机构允许批准在结构和功能上与其参比产品不同的生物仿制药，但这些差异不应具有任何临床意义。为了识别这些重大差异，必须对关键产品属性进行实时表征，并在存储后直到产品有效期内进行表征。在本研究中，对在印度销售的两个 Bvz 生物仿制药品牌（Bio-1 和 Bio-2）进行了评估，并与参考产品 Avastin® 进行比较，以评估它们的相似程度。使用包括 LC-ESI-QTOF、MALDI-TOF、FTIR-ATR、iCIEF、rCE、nrCE、UV280 和 RP-HPLC 在内的正交技术对生物仿制药和参比产物进行全面的物理化学表征。此外，所研究的 Bvz 制剂经受热（高温 50 ± 2 °C）、化学（酸性 pH 3.0 ± 0.2、中性 pH 7.0 ± 0.2 和碱性 pH 10.0 ± 0.2）和机械（搅拌 200 rpm）的各种应力条件下，以进行比较稳定性评估。使用远紫外圆二色谱（CD）检测和定量天然蛋白质二级结构的任何变化，表明在暴露于高温和高 pH 值时，Bio-1 和 Bio-2 中的天然反平行 β 折叠构象平均分别损失 15% 和 11%。此外，使用 SEC-MALS 定量作为高温和搅拌函数形成的共价或非共价聚集体。

"点击查看英文标题和摘要"

Comparative stability study and aggregate analysis of Bevacizumab marketed formulations using advanced analytical techniques

Bevacizumab (Bvz) is the most preferred recombinant humanized monoclonal antibody in biosimilar development due to its prominence as a standard treatment in the oncology space. Therapeutic monoclonal antibodies are typically more complex and unlikely to produce a replica. As a result, regulatory agencies allow approval of biosimilars that differ structurally and functionally from their reference product, but these differences should not have any clinical significance. To identify these significant discrepancies, it is essential to perform a thorough characterization of critical product attributes both in real-time and after storage until the product's expiration. In the present study, two Bvz biosimilar brands (Bio-1 and Bio-2) marketed in India were evaluated and compared with the reference product Avastin® to assess their degree of similarity. A comprehensive physicochemical characterization of biosimilars and reference product was performed using orthogonal techniques including LC-ESI-QTOF, MALDI-TOF, FTIR-ATR, iCIEF, rCE, nrCE, UV280, and RP-HPLC. Furthermore, Bvz formulations under study were subjected to various stress conditions of thermal (elevated temperature 50 ± 2 °C), chemical (acidic pH 3.0 ± 0.2, neutral pH 7.0 ± 0.2, and basic pH 10.0 ± 0.2), and mechanical (agitation 200 rpm) for comparative stability evaluation. Any alteration in the secondary structure of the native protein was detected and quantified using far-UV circular dichroism (CD), indicating an average of 15% and 11% loss in native antiparallel β-sheet conformation respectively in Bio-1 and Bio-2 upon exposure to elevated temperature and high pH. Additionally, covalent or non-covalent aggregates formed as a function of elevated temperature and agitation were quantified using SEC-MALS.

更新日期：2023-08-28

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文