在大规模生产和分析基于 mRNA-LNP 的疫苗过程中监测 RNase 的重要性。

IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL
Robbe Van Pottelberge, Roman Matthessen, Shauna Salem, Ben Goffin, Nancee Oien, Pratima Bharti, David Ripley
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引用次数: 0

摘要

核糖核酸酶(RNase)在自然界无处不在,能够裂解多种多核苷酸。虽然对无菌生产中的微生物和病毒污染进行了深入研究和控制,但对生产设施中的核糖核酸酶却没有标准化的评估方法。自 COVID-19 大流行以来,基于 mRNA-LNP 的疫苗已成为常规大规模生产的一部分。mRNA 的不稳定性为保障基于 mRNA - 脂质纳米粒子 (LNP) 的疫苗或疗法的工作功效带来了新的挑战,因为配制过程中 RNase 的存在可能会对 mRNA 的完整性产生深远影响。本文介绍了在 LNP 药物产品配制和分析过程中评估 RNase 污染的经验教训。利用灵敏的检测方法,研究了 mRNA-LNPs 生产过程中可能存在的 RNase。此外,用于测量 mRNA 完整性的毛细管凝胶电泳 (CGE) 数据证明了活性 mRNA 物质的质量和合适的 RNase 控制策略的重要性。本文介绍的结果和案例将为基于 mRNA-LNP 的疫苗和疗法的评估和控制策略铺平道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Importance of RNase monitoring during large-scale manufacturing and analysis of mRNA-LNP based vaccines.

Ribonucleases (RNases) are ubiquitous in nature, being able to cleave a wide range of polyribonucleotides. While the presence of microbial and viral contamination in sterile manufacturing is highly studied and controlled, there are no standardized practices for evaluating RNase in the production facility. Since the COVID-19 pandemic, mRNA-LNP based vaccines have become part of routine large-scale manufacturing. The unstable nature of mRNA poses new challenges to safeguard the working efficacy of mRNA - Lipid nanoparticle (LNP) based vaccines or therapeutics, where the presence of RNase in the formulation process could have a profound impact on the mRNA integrity. In this article, lessons learned are presented with respect to the evaluation of RNase contamination during LNP drug product formulation and analysis. Using sensitive detection methods, the potential presence of RNase in the manufacturing of mRNA-LNPs was investigated. Additionally, capillary gel electrophoresis (CGE) data, used to measure mRNA integrity, demonstrate the quality of the active mRNA substance and importance of suitable RNase control strategies. The results and cases presented in this paper should pave the way forward for evaluation and control strategies dedicated to mRNA-LNP based vaccines and therapeutics.

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来源期刊
CiteScore
7.30
自引率
13.20%
发文量
367
审稿时长
33 days
期刊介绍: The Journal of Pharmaceutical Sciences will publish original research papers, original research notes, invited topical reviews (including Minireviews), and editorial commentary and news. The area of focus shall be concepts in basic pharmaceutical science and such topics as chemical processing of pharmaceuticals, including crystallization, lyophilization, chemical stability of drugs, pharmacokinetics, biopharmaceutics, pharmacodynamics, pro-drug developments, metabolic disposition of bioactive agents, dosage form design, protein-peptide chemistry and biotechnology specifically as these relate to pharmaceutical technology, and targeted drug delivery.
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