补料优化降低抗体生产过程中宿主细胞蛋白残留的研究

目的:通过上游工艺中补料培养基优化以降低单克隆抗体生产中的宿主细胞蛋白(HCP)水平。方法:本文在3 L反应器的工艺开发过程中考察了不同的商品化补料培养基和细胞接种密度对HCP水平的影响,筛选出最优条件后,进行了补料工艺的优化和金属离子的添加试验,最后将优化后的工艺放大至200 L中试规模。结果:在小试阶段发现Cellvento 4Feed可以显著降低HCP,同时CuSO4可以进一步促进HCP降低的水平,最终将工艺放大至200 L中试进行生产并取得了相似的结果,验证了工艺的稳定性和可放大性,中试规模的HCP水平相比最初的工艺降低了65%左右。结论:补料培养基优化可以有效降低细胞对HCP的比生产速率,使收获液中整体的HCP水平显著下降。

Studies on Reducing Host Cell Protein by Feed Medium Optimization during Monoclonal Antibody Production Process

ABSTRACT Objective: Reduce host cell protein (HCP) level in monoclonal production process by feed medium optimization during upstream process. Methods: This work investigated the performance of different commercial feed media and different inoculation densities in 3 L bioreactors. Further study with feed medium optimization and supplement of inorganic salt was conducted based on the best combination. The final process was scaled-up to 200 L pilot production. Results: During the bench scale study, Cellvento 4Feed was proved to reduce HCP significantly and CuSO₄ can further reduce HCP. This process was scaled up to 200 L pilot production and similar results were achieved, which validated the robustness and scalability of the process. HCP level was reduced around 65% than the initial process. Conclusion: Optimization of feed medium could reduce the specific production rate of HCP of cells, and finally the HCP level in the harvest liquid is reduced significantly.