重组蛋白产业化中内毒素的去除、检测及限值

Removal, detection, and limits of endotoxin in the industry of recombinant proteins

摘要:

随着合成生物技术的发展，重组蛋白将在医疗领域发挥重要作用。重组蛋白规模化生产是其在各领域普及、发展的基础。规模化生产过程中需要对内毒素进行去除与检测，将其在终产品中的含量降到安全水平。针对不同重组蛋白产品制定严格的内毒素限值要求是安全性评价的重要一环。本文综述了内毒素的致病性，讨论了重组蛋白生产过程中内毒素的去除及测定方法，介绍了生物制品、医疗器械、人用重组DNA制品等行业对内毒素检测限值的要求，重点介绍了重组蛋白注射产品的内毒素限值要求，明确无论重组蛋白表达宿主是否为细菌，均需对注射用重组蛋白的终产品进行内毒素检测，并需符合相关行业标准要求。本文将为重组蛋白规模化生产过程中内毒素的相关研究提供参考。

Abstract:

With the advancement of synthetic biology, recombinant proteins are poised to play a significant role in medical applications. The scaled manufacturing is a pillar for the extensive application and development of recombinant proteins across various fields. In the large-scale production process of recombinant proteins, the removal and detection of endotoxins are essential to reduce their levels to safe thresholds in the final products. Currently, establishing stringent endotoxin limits for different recombinant protein products is a crucial aspect of safety assessment. This review begins by shedding light on the pathogenicity of endotoxins and discusses the methods for the removal and determination of endotoxins during the production processes of recombinant proteins. Subsequently, this review summarizes the endotoxin limits in industries such as biologics, medical devices, and human recombinant DNA products, particularly those in recombinant protein injection products. It is highlighted that regardless of whether the hosts for recombinant protein expression are bacteria or not, endotoxin testing is required for the final products of injectable recombinant proteins, and compliance with relevant industry standards is necessary. This review aims to provide a reference for the research on endotoxins in the large-scale production process of recombinant proteins.