生產(chǎn)用一次性組件與容器密閉系統(tǒng)中的可提取物和浸出物（extractable&leachable，E&L）安全性評(píng)估是藥品上市申報(bào)的重要環(huán)節(jié)之一。E&L的毒理學(xué)評(píng)價(jià)是其安全性評(píng)估的重點(diǎn)內(nèi)容，目前尚未有E&L毒理學(xué)評(píng)價(jià)的系統(tǒng)性指導(dǎo)法規(guī)，特別是多個(gè)毒理數(shù)據(jù)來(lái)源的合理選擇，以及毒理數(shù)據(jù)缺乏的問(wèn)題，是E&L安全性評(píng)估的難點(diǎn)。基于E&L安全性評(píng)估，重點(diǎn)介紹了安全閾值的確定策略，包括每日允許最大暴露量和日攝入量計(jì)算、多層次毒理學(xué)關(guān)注閾值的選擇；相關(guān)毒理數(shù)據(jù)的選擇和評(píng)價(jià)，包括毒理學(xué)觀測(cè)指標(biāo)和試驗(yàn)選擇，以及關(guān)鍵毒性效應(yīng)的選擇。并結(jié)合實(shí)際事例，為解決E&L研究中安全性評(píng)估問(wèn)題提供新思路，為藥品研發(fā)及生產(chǎn)企業(yè)提供借鑒。

The safety assessment of extractable & leachable (E&L) in single use system, applied in manufacturing process and container closure system for drug product, is a vital part of new drug application or biologic license application. Toxicological evaluation of E&L is of importance in E&L safety evaluation. There are no systematic guidelines for E&L toxicological evaluation, especially for toxicological data selection, which poses a great challenge for E&L safety evaluation. Based on the E&L safety assessment, this paper focuses on the establishment strategy of safety threshold, including permitted daily exposure and acceptable intake calculation, the selection of multi-level threshold toxicological concern; the selection and evaluation of key toxicological data, including toxicological observation indicators and rational assay selection, and the identification of "critical effects". Here, we combined the systematic introduction of E&L toxicology evaluation with actual cases, which provides a new insight to solve the problem in E&L research and gives recommends and assistance for drug development and production enterprises.