已上市化學藥品變更研究技術指導原則（一）

本指導原則主要用(yong)于指導藥品生(sheng)產企業開展已上市(shi)(shi)化(hua)學(xue)藥品的(de)(de)變更(geng)(geng)研(yan)究。變更(geng)(geng)是指對(dui)已獲準上市(shi)(shi)化(hua)學(xue)藥品在(zai)生(sheng)產、質控(kong)、使用(yong)條(tiao)件等(deng)諸(zhu)多方面(mian)提出(chu)的(de)(de)涉及來源、方法(fa)、控(kong)制條(tiao)件等(deng)方面(mian)的(de)(de)變化(hua)。這些變化(hua)可(ke)能影響到藥品的(de)(de)安全性(xing)、有效性(xing)和質量可(ke)控(kong)性(xing)。變更(geng)(geng)研(yan)究是針對(dui)擬進行的(de)(de)變化(hua)所(suo)開展的(de)(de)研(yan)究驗證工作。
        目(mu)前本指導原(yuan)則涵蓋的變(bian)(bian)(bian)(bian)更(geng)(geng)及變(bian)(bian)(bian)(bian)更(geng)(geng)研(yan)究包括以下項目(mu)：原(yuan)料(liao)藥(yao)(yao)生產(chan)(chan)(chan)工藝(yi)變(bian)(bian)(bian)(bian)更(geng)(geng)、藥(yao)(yao)品(pin)制劑處方(fang)中已(yi)有藥(yao)(yao)用(yong)要求的輔料(liao)和(he)制備(bei)工藝(yi)變(bian)(bian)(bian)(bian)更(geng)(geng)、注冊(ce)標準變(bian)(bian)(bian)(bian)更(geng)(geng)、規格變(bian)(bian)(bian)(bian)更(geng)(geng)、有效期和(he)貯(zhu)藏條件變(bian)(bian)(bian)(bian)更(geng)(geng)、藥(yao)(yao)品(pin)的包裝材(cai)料(liao)和(he)容器變(bian)(bian)(bian)(bian)更(geng)(geng)、進口藥(yao)(yao)品(pin)產(chan)(chan)(chan)地變(bian)(bian)(bian)(bian)更(geng)(geng)、進口原(yuan)料(liao)藥(yao)(yao)產(chan)(chan)(chan)地和(he)進口藥(yao)(yao)品(pin)所用(yong)原(yuan)料(liao)藥(yao)(yao)產(chan)(chan)(chan)地變(bian)(bian)(bian)(bian)更(geng)(geng)、變(bian)(bian)(bian)(bian)更(geng)(geng)國內生產(chan)(chan)(chan)藥(yao)(yao)品(pin)制劑的原(yuan)料(liao)藥(yao)(yao)產(chan)(chan)(chan)地等研(yan)究。
        本(ben)指(zhi)導(dao)原則(ze)僅從(cong)技術(shu)角度闡述對產(chan)品(pin)(pin)進行變(bian)(bian)(bian)更(geng)(geng)時，應(ying)進行的(de)(de)(de)相(xiang)關(guan)研(yan)究(jiu)驗證(zheng)工(gong)作。藥(yao)品(pin)(pin)生(sheng)(sheng)(sheng)產(chan)企業(ye)需按照(zhao)本(ben)指(zhi)導(dao)原則(ze)的(de)(de)(de)相(xiang)關(guan)技術(shu)要(yao)(yao)(yao)求(qiu)(qiu)，開(kai)展(zhan)變(bian)(bian)(bian)更(geng)(geng)研(yan)究(jiu)驗證(zheng)工(gong)作，在完成相(xiang)關(guan)工(gong)作后，應(ying)根據《藥(yao)品(pin)(pin)注冊(ce)管理辦法》中(zhong)的(de)(de)(de)有(you)(you)(you)(you)關(guan)要(yao)(yao)(yao)求(qiu)(qiu)，向(xiang)各級食品(pin)(pin)藥(yao)品(pin)(pin)監管部門提出補充申(shen)(shen)請。為(wei)便于把握變(bian)(bian)(bian)更(geng)(geng)可(ke)(ke)(ke)能對產(chan)品(pin)(pin)安(an)(an)(an)全(quan)性(xing)(xing)、有(you)(you)(you)(you)效(xiao)(xiao)性(xing)(xing)和質量可(ke)(ke)(ke)控性(xing)(xing)產(chan)生(sheng)(sheng)(sheng)的(de)(de)(de)影(ying)響(xiang)，本(ben)指(zhi)導(dao)原則(ze)對所述及(ji)的(de)(de)(de)變(bian)(bian)(bian)更(geng)(geng)劃(hua)分為(wei)三類：I類變(bian)(bian)(bian)更(geng)(geng)屬(shu)于微(wei)小變(bian)(bian)(bian)更(geng)(geng)，對產(chan)品(pin)(pin)安(an)(an)(an)全(quan)性(xing)(xing)、有(you)(you)(you)(you)效(xiao)(xiao)性(xing)(xing)和質量可(ke)(ke)(ke)控性(xing)(xing)基本(ben)不產(chan)生(sheng)(sheng)(sheng)影(ying)響(xiang)；II類變(bian)(bian)(bian)更(geng)(geng)屬(shu)于中(zhong)度變(bian)(bian)(bian)更(geng)(geng)，需要(yao)(yao)(yao)通過(guo)相(xiang)應(ying)的(de)(de)(de)研(yan)究(jiu)工(gong)作證(zheng)明變(bian)(bian)(bian)更(geng)(geng)對產(chan)品(pin)(pin)安(an)(an)(an)全(quan)性(xing)(xing)、有(you)(you)(you)(you)效(xiao)(xiao)性(xing)(xing)和質量可(ke)(ke)(ke)控性(xing)(xing)不產(chan)生(sheng)(sheng)(sheng)影(ying)響(xiang)；III類變(bian)(bian)(bian)更(geng)(geng)屬(shu)于較大變(bian)(bian)(bian)更(geng)(geng)，需要(yao)(yao)(yao)通過(guo)系列的(de)(de)(de)研(yan)究(jiu)工(gong)作證(zheng)明變(bian)(bian)(bian)更(geng)(geng)對產(chan)品(pin)(pin)安(an)(an)(an)全(quan)性(xing)(xing)、有(you)(you)(you)(you)效(xiao)(xiao)性(xing)(xing)和質量可(ke)(ke)(ke)控性(xing)(xing)沒有(you)(you)(you)(you)產(chan)生(sheng)(sheng)(sheng)負面影(ying)響(xiang)。變(bian)(bian)(bian)更(geng)(geng)類別劃(hua)分考(kao)慮(lv)了(le)目前藥(yao)品(pin)(pin)注冊(ce)管理對補充申(shen)(shen)請的(de)(de)(de)有(you)(you)(you)(you)關(guan)規(gui)定，并參考(kao)了(le)國外(wai)的(de)(de)(de)有(you)(you)(you)(you)關(guan)技術(shu)要(yao)(yao)(yao)求(qiu)(qiu)，目的(de)(de)(de)是(shi)為(wei)了(le)幫助藥(yao)品(pin)(pin)生(sheng)(sheng)(sheng)產(chan)企業(ye)有(you)(you)(you)(you)針對性(xing)(xing)地開(kai)展(zhan)變(bian)(bian)(bian)更(geng)(geng)研(yan)究(jiu)，并將研(yan)究(jiu)結果總結成相(xiang)應(ying)的(de)(de)(de)資(zi)料(liao)，向(xiang)管理部門提出相(xiang)應(ying)的(de)(de)(de)補充申(shen)(shen)請。
        本指(zhi)導原(yuan)(yuan)則所指(zhi)變更是針對(dui)已上市化(hua)(hua)學(xue)藥(yao)品提出的(de)。因此(ci)，變更及(ji)(ji)變更研(yan)究(jiu)(jiu)工(gong)作(zuo)(zuo)(zuo)應以(yi)既(ji)往藥(yao)品注(zhu)(zhu)冊階段以(yi)及(ji)(ji)實際(ji)生(sheng)產過程中(zhong)的(de)研(yan)究(jiu)(jiu)和數(shu)據(ju)積(ji)(ji)累(lei)為基(ji)礎(chu)。注(zhu)(zhu)冊階段的(de)研(yan)究(jiu)(jiu)工(gong)作(zuo)(zuo)(zuo)越(yue)(yue)系統、深入(ru)，生(sheng)產過程中(zhong)積(ji)(ji)累(lei)的(de)數(shu)據(ju)越(yue)(yue)充(chong)分(fen)，對(dui)上市后(hou)的(de)變更研(yan)究(jiu)(jiu)越(yue)(yue)有(you)幫(bang)助(zhu)。本指(zhi)導原(yuan)(yuan)則中(zhong)提及(ji)(ji)的(de)各(ge)項研(yan)究(jiu)(jiu)工(gong)作(zuo)(zuo)(zuo)的(de)具體要求可參見已頒布的(de)相關化(hua)(hua)學(xue)藥(yao)物研(yan)究(jiu)(jiu)技術指(zhi)導原(yuan)(yuan)則，或其(qi)他相關技術指(zhi)導原(yuan)(yuan)則。如果(guo)通(tong)過其(qi)他科學(xue)的(de)研(yan)究(jiu)(jiu)工(gong)作(zuo)(zuo)(zuo)所得到(dao)的(de)結論亦能證(zheng)明(ming)變更對(dui)藥(yao)品的(de)安全性(xing)、有(you)效性(xing)和質(zhi)量可控(kong)性(xing)不(bu)產生(sheng)負面(mian)影響(xiang)，在提供充(chong)分(fen)依據(ju)的(de)基(ji)礎(chu)上，可以(yi)不(bu)必完全按照本指(zhi)導原(yuan)(yuan)則的(de)要求進行變更研(yan)究(jiu)(jiu)。

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