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Effect of change in cell substrate on the critical quality attributes of L-Zagreb Mumps vaccine manufactured using parallel plate bioreactor.
Biologicals ( IF 1.7 ) Pub Date : 2020-08-24 , DOI: 10.1016/j.biologicals.2020.07.008
Ravindra Muley 1 , Rajeev Dhere 1
Affiliation  

Leningrad-Zagreb strain of mumps vaccine virus was grown on two different cell substrates viz. MRC-5 cells and Vero cells besides its original cell substrate i.e. Chicken Embryo Cells. Homogeneous virus pools prepared from each set of experiments were then lyophilized as per standard in-house protocol.

Critical Quality Attributes (CQAs) such as the titer of the bulk vaccine and potency and stability of the lyophilized vaccine were then estimated using the CCID50 method to understand the lyophilization losses and thermal losses respectively in the vaccine. Another CQA viz. the genetic homogeneity of the vaccine was also tested using the single base extension method for identifying the nucleotides present at the three known locations of single nucleotide polymorphism (SNP).

Comparison of CQA results across different cell substrates indicated encouraging results for Vero cell grown L-Zagreb virus compared to the MRC-5 cells grown L-Zagreb mumps virus. Significant improvement in productivity was also observed in the dynamic culture conditions compared to the static culture conditions.

Progressive work in this research area can lead to development of a cGMP manufacturing process for mumps vaccine with easy scale up potential in future.



中文翻译:

细胞底物变化对使用平行板生物反应器生产的 L-萨格勒布腮腺炎疫苗关键质量属性的影响。

腮腺炎疫苗病毒的列宁格勒-萨格勒布株在两种不同的细胞基质上生长,即。MRC-5 细胞和 Vero 细胞,除了其原始细胞基质,即鸡胚胎细胞。然后按照标准内部方案冻干从每组实验制备的均质病毒库。

然后使用 CCID 50方法估计关键质量属性 (CQA),例如散装疫苗的滴度以及冻干疫苗的效力和稳定性,以分别了解疫苗中的冻干损失和热损失。另一个 CQA 即。还使用单碱基延伸方法测试了疫苗的遗传同质性,以鉴定存在于单核苷酸多态性 (SNP) 的三个已知位置的核苷酸。

不同细胞底物的 CQA 结果比较表明,与 MRC-5 细胞培养的 L-萨格勒布腮腺炎病毒相比,Vero 细胞培养的 L-萨格勒布病毒获得了令人鼓舞的结果。与静态培养条件相比,在动态培养条件下也观察到生产力的显着提高。

该研究领域的进展工作可能会导致腮腺炎疫苗的 cGMP 生产工艺的开发,未来很容易扩大规模。

更新日期:2020-10-06
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