Ng Siemon, Gisonni-Lex Lucy, Azizi Ali
a Microbiology & Virology Platform , Department of Analytical Research & Development North America, Sanofi Pasteur , Toronto , Ontario , Canada.
Hum Vaccin Immunother. 2017 Jul 3;13(7):1669-1672. doi: 10.1080/21645515.2017.1295191. Epub 2017 Feb 23.
The genetic stability of cell lines is a critical analytical attribute required to demonstrate the quality of cells over time. During cell passage, mutations can arise in the genomic DNA, potentially leading to changes in the final vaccine product. The identity and integrity of master cell banks, extended cell banks, complementing cell lines or recombinant cell lines expressing transgenes has to be tested throughout the production process by the vaccine manufacturer. Over the past few years, the traditional methods for evaluation of genetic stability have been replaced with molecular approaches including quantitative PCR, digital PCR and high throughput sequencing. However, these molecular-based approaches are used in research laboratories and not within a GMP-compliant environment. In this article, we briefly discuss some opportunities and challenges in characterization of the genetic stability of vaccine cell lines with these molecular-based approaches.
细胞系的遗传稳定性是证明细胞随时间推移的质量所需的关键分析属性。在细胞传代过程中，基因组DNA可能会发生突变，这可能导致最终疫苗产品发生变化。疫苗生产商必须在整个生产过程中对主细胞库、扩展细胞库、互补细胞系或表达转基因的重组细胞系的身份和完整性进行检测。在过去几年中，传统的遗传稳定性评估方法已被包括定量PCR、数字PCR和高通量测序在内的分子方法所取代。然而，这些基于分子的方法仅用于研究实验室，并未用于符合GMP标准的环境中。在本文中，我们简要讨论了使用这些基于分子的方法表征疫苗细胞系遗传稳定性时的一些机遇和挑战。
