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Pressure-dependent fouling behavior during sterile filtration of mRNA-containing lipid nanoparticles
Biotechnology and Bioengineering ( IF 3.8 ) Pub Date : 2022-07-29 , DOI: 10.1002/bit.28200
Kevork Oliver Messerian 1 , Anton Zverev 2 , Jack F Kramarczyk 2 , Andrew L Zydney 1
Affiliation  

The COVID-19 pandemic has generated growing interest in the development of mRNA-based vaccines and therapeutics. However, the size and properties of the lipid nanoparticles (LNPs) used to deliver the nucleic acids can lead to unique phenomena during manufacturing that are not typical of other biologics. The objective of this study was to develop a more fundamental understanding of the factors controlling the performance of sterile filtration of mRNA-LNPs. Experimental filtration studies were performed with a Moderna mRNA-LNP solution using a commercially available dual-layer polyethersulfone sterile filter, the Sartopore 2 XLG. Unexpectedly, increasing the transmembrane pressure (TMP) from 2 to 20 psi provided more than a twofold increase in filter capacity. Also surprisingly, the effective resistance of the fouled filter decreased with increasing TMP, in contrast to the pressure-independent behavior expected for an incompressible media and the increase in resistance typically seen for a compressible fouling deposit. The mRNA-LNPs appear to foul the dual-layer filter by blocking the pores in the downstream sterilizing-grade membrane layer, as demonstrated both by scanning electron microscopy and derivative analysis of filtration data collected for the two layers independently. These results provide important insights into the mechanisms governing the filtration of mRNA-LNP vaccines and therapeutics.

中文翻译:

含 mRNA 脂质纳米颗粒无菌过滤过程中的压力依赖性结垢行为

COVID-19 大流行引起了人们对开发基于 mRNA 的疫苗和疗法的兴趣。然而,用于递送核酸的脂质纳米颗粒 (LNP) 的大小和性质可能会导致制造过程中出现其他生物制剂不典型的独特现象。本研究的目的是更基本地了解控制 mRNA-LNP 无菌过滤性能的因素。使用市售双层聚醚砜无菌过滤器 Sartopore 2 XLG 使用 Moderna mRNA-LNP 溶液进行实验性过滤研究。出乎意料的是,将跨膜压力 (TMP) 从 2 增加到 20 psi 可使过滤器容量增加两倍以上。同样令人惊讶的是,结垢过滤器的有效阻力随着 TMP 的增加而降低,这与不可压缩介质预期的与压力无关的行为以及可压缩结垢沉积物通常看到的阻力增加形成对比。mRNA-LNP 似乎通过阻塞下游灭菌级膜层中的孔来污染双层过滤器,如扫描电子显微镜和独立收集的两层过滤数据的衍生分析所证明的那样。这些结果为控制 mRNA-LNP 疫苗和治疗剂的过滤机制提供了重要的见解。mRNA-LNP 似乎通过阻塞下游灭菌级膜层中的孔来污染双层过滤器,如扫描电子显微镜和独立收集的两层过滤数据的衍生分析所证明的那样。这些结果为控制 mRNA-LNP 疫苗和治疗剂的过滤机制提供了重要的见解。mRNA-LNP 似乎通过阻塞下游灭菌级膜层中的孔来污染双层过滤器,如扫描电子显微镜和独立收集的两层过滤数据的衍生分析所证明的那样。这些结果为控制 mRNA-LNP 疫苗和治疗剂的过滤机制提供了重要的见解。
更新日期:2022-07-29
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