為了保證化學藥品注射劑的安全性,需加強對所用直接接觸藥品包材的熱原的有效控制。通過對國內外相關法規(guī)及指南的匯總比較,結合審評工作實踐,對包材除熱原常用工藝及相關驗證要求進行探討。企業(yè)應基于包材類型及材料的性質,對除熱原工藝進行研究和驗證,證明其去除熱原的能力滿足要求。常見的玻璃包材除熱原工藝為干熱處理,常見的膠塞除熱原工藝為沖洗除熱原,塑料包材通常通過粒料內毒素控制、高溫吹塑工藝及生產(chǎn)環(huán)境來保障細菌內毒素符合要求。在除熱原驗證中,應合理選擇內毒素指示劑并制訂除熱原驗證標準,標準通常為內毒素至少下降3個對數(shù)單位。

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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