| 郭莎,张峰,刘春雨,于传飞,李萌,王文波,付志浩,俞小娟,王兰.过滤对一种IgG2亚型EGFR单抗中不溶性微粒的影响[J].中国药事,2018,32(9):1245-1250 |
| 过滤对一种IgG2亚型EGFR单抗中不溶性微粒的影响 |
| Effect of Filtration on Sub-visible Particles in an EGFR Monoclonal Antibody of IgG2 Subclass |
| 投稿时间：2018-05-30 |
| DOI：10.16153/j.1002-7777.2018.09.15 |
| 中文关键词: 单克隆抗体 过滤 不溶性微粒 蛋白聚体 微流数字成像技术 |
| 英文关键词: monoclonal antibody filtration sub-visible particle protein aggregate microflow digital imaging |
| 基金项目:重大新药创制恶性肿瘤治疗的单抗类生物类似药质量评价研究（编号2018ZX09736016-007） |
| 作者 | 单位 | E-mail | | 郭莎 | 中国食品药品检定研究院单克隆抗体产品室, 卫生部生物技术产品检定及标准化重点实验室, 北京 102629 | | | 张峰 | 中国食品药品检定研究院单克隆抗体产品室, 卫生部生物技术产品检定及标准化重点实验室, 北京 102629 | | | 刘春雨 | 中国食品药品检定研究院单克隆抗体产品室, 卫生部生物技术产品检定及标准化重点实验室, 北京 102629 | | | 于传飞 | 中国食品药品检定研究院单克隆抗体产品室, 卫生部生物技术产品检定及标准化重点实验室, 北京 102629 | | | 李萌 | 中国食品药品检定研究院单克隆抗体产品室, 卫生部生物技术产品检定及标准化重点实验室, 北京 102629 | | | 王文波 | 中国食品药品检定研究院单克隆抗体产品室, 卫生部生物技术产品检定及标准化重点实验室, 北京 102629 | | | 付志浩 | 中国食品药品检定研究院单克隆抗体产品室, 卫生部生物技术产品检定及标准化重点实验室, 北京 102629 | | | 俞小娟 | 中国食品药品检定研究院单克隆抗体产品室, 卫生部生物技术产品检定及标准化重点实验室, 北京 102629 | | | 王兰 | 中国食品药品检定研究院单克隆抗体产品室, 卫生部生物技术产品检定及标准化重点实验室, 北京 102629 | wanglan@nifdc.org.cn |
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| 中文摘要: |
| 目的：探讨过滤操作对一种免疫球蛋白G2（immunoglobin G2，IgG2）亚型表皮生长因子受体（epidermal growth factor receptor，EGFR）单克隆抗体（单抗）生物类似药（similar biotherapeutic product，SBP）候选药中不溶性微粒的影响。方法：利用微流数字成像（microflow digital imaging，MDI）技术对某厂家生产的IgG2亚型EGFR单抗SBP候选药与其原研药（reference biotherapeutic product，RBP）中不同粒径的不溶性微粒进行比较；采用0.22 μm的滤器对EGFR单抗SBP候选药进行过滤，并采用MDI法立即对不同粒径和性质的不溶性微粒进行检测和分析；再将过滤后的EGFR单抗SBP候选药在室温静置2 h，并采用MDI法对不同粒径和性质的不溶性微粒进行检测和分析。结果：某IgG2亚型EGFR单抗SBP候选药中不同粒径的不溶性微粒数量明显高于RBP；用0.22 μm的滤器过滤后，EGFR单抗SBP候选药中的不溶性微粒数由8.51×105粒·mL-1降为1.52×104粒·mL-1，且主要成分蛋白聚体、气泡和纤维均明显减少；室温静置2 h后，其中的不溶性微粒数由1.52×104粒·mL-1增加至3.23×104粒·mL-1，且增加的微粒主要为蛋白聚体。结论：与原研药相比，该EGFR单抗SBP候选药蛋白聚体水平较高，过滤后有明显改善，但随着放置时间延长，蛋白聚体含量又有明显增加。这提示我们需加强研发，以提高SBP候选药的产品质量、安全性和有效性。 |
| 英文摘要: |
| Objective: To investigate the effect of filtration on sub-visible particles in a similar biotherapeutic product (SBP) candidate for EGFR monoclonal antibody (mAb) of IgG2 subclass.Methods: Microflow digital imaging (MDI) was used to compare the sub-visible particles of different diameters in the EGFR mAb SBP candidate of IgG2 subclass with those in the corresponding reference biotherapeutic product (RBP). Then the EGFR mAb SBP candidate drug was filtered by a 0.22 μm filter, and the sub-visible particles of different diameters and properties were immediately detected and analyzed by the MDI method. The sub-visible particles of different diameters and properties were tested again immediately after filtered EGFR mAb SBP candidate was kept at room temperature for 2 h.Results: The number of sub-visible particles with different diameters of the IgG2 EGFR mAb SBP candidate was significantly higher than that of the corresponding RBP. After filtration with 0.22 μm filter, the number of sub-visible particles of the EGFR mAb SBP candidate decreased from 8.51×105 particles·mL-1 to 1.52×104 particles·mL-1, and the number of the main components, such as protein aggregates, bubbles and fibers obviously decreased. After having been kept at room temperature for 2h, sub-visible particles increased from 1.52×104 particles·mL-1 to 3.23×104 particles·mL-1 and the increased particles were mainly protein aggregates.Conclusion: Compared with RBP, sub-visible particles in EGFR mAb SBP candidate were significantly higher. The sub-visible particles substantially decreased after filtration, but with the time duration increased, the protein aggregates increased too, indicating that it is necessary to strengthen the research and development in order to improve the quality, safety and effectiveness of SBP candidates. |
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