为了保证化学药品注射剂的安全性,需加强对所用直接接触药品包材的热原的有效控制。通过对国内外相关法规及指南的汇总比较,结合审评工作实践,对包材除热原常用工艺及相关验证要求进行探讨。企业应基于包材类型及材料的性质,对除热原工艺进行研究和验证,证明其去除热原的能力满足要求。常见的玻璃包材除热原工艺为干热处理,常见的胶塞除热原工艺为冲洗除热原,塑料包材通常通过粒料内毒素控制、高温吹塑工艺及生产环境来保障细菌内毒素符合要求。在除热原验证中,应合理选择内毒素指示剂并制订除热原验证标准,标准通常为内毒素至少下降3个对数单位。

In order to ensure the safety of chemical injections, it is necessary to strengthen the effective control of pyrogen in direct contact with drug packaging materials. Based on the summary and comparison of domestic and foreign regulations and guidelines,combined with the review practice, the common process of pyrogen removal of packaging materials and related verification requirements are discussed in this paper. The process used to remove pyrogen from packaging materials mainly depends on the types and properties of materials. The process of depyrogenation should be studied and verified to prove that the ability of depyrogenation meets the requirements. The common depyrogenation process of glass packaging materials is dry heat treatment, the common rubber plug depyrogenation process is washing, and plastic packaging materials are usually controlled by granule endotoxin, high temperature blow molding process and production environment to ensure that the bacterial endotoxin meets the requirements. In the verification of depyrogenation, endotoxin indicators should be reasonably selected and the verification criteria for depyrogenation should be established. The usually acceptable standard is a decrease of at least 3 logarithmic units of endotoxin.

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