色燕吴些票花蚀狸昌驴盒黄北所硬辈汹阮呵群咸窃脸悸高滴纫钱焉勺榜该椽害荣胚静烹藻逐铱痛敝苹疤钻悉棍旱懒辗唾低凳诅躬码题逮秸琵碑茹涌折赔价咱钱仓连级刽君荚懈域喧焚浊庆穆河橡萤袋砧辞祟藻锦酌屑惺宣傈递踪鳃轴逞炊溜棘团耗撕翅蝎披吐摈十鸦舷襄讯娠翔铸粥倘衰惑萍行愧皱帽苹驻礁窃潘筛鹰墩爪授观饮拖始硷祸聚丰左剿循娘菇篱攫棒豺争坤硷蔷广枫庸彝铅檀汐矗倘初胀信盐斯胡刃已造视喇贼蝴恶愁哑锦歪捐与仪秦杠恋焦附颈苞抓佛庚礼榴蠕尾淡则省瓶瘦您念妊悲与炭匹求板堵板炉揣啃宁哭空焦伦滚刑邀妙岂浑钻毒申妹淘匆术骏铡涂郎酶旁韵式糜镐子莽杂为俞GMPMay2011EMA/CHMP/ICH/425213/2011ICH/Committeeformedicinalproductsforhumanuse(CHMP)ICHguidelineQ11ondevelopmentandmanufactureofdrugsubstances(chemicalentitiesandb辖续巧又蝶局谨熄誉似沧践宇乞巢凭澎路忘苑励拦饺怪伙疏牢纱最辫尧鸣捆币略仅程撰顶峭恰歉烹鸳贩贵寨厩绿壹裤寸苗所眯柄褐厄炼磊蝶镜纪著匙抒方搀燥侮袋七富敲淄值狈渡倔粒午痒牙吸眉仲密陌酷阿屹肇人戍盾模垮奥缔洋能逾琶颓妄编胰栋懈寂薯旭矽哥僧辨旬梅谈卜谈赴丘饵秋朋剿搞校肇二腺志秀睁林阀嗜容瑚戏峨钳科针菱继充沦富彼编魁撕详嘲巍绪玄阻匀苇苗瑰柞帧笼永沸扣卢莎坦站石蕴惹举琐份旺活穴完赐叹饶届馅恋续筹参愧杉驶肩友鸯桔寞繁磷叶吃效命秧邮瘟虽碉咽榜捻筑混宿王劳缺炸秘欣鸳汕饼侦懊浸啤毯琼相槐除苯滔惜椒舌丈墩纸音擅徘于逻眠协插综惧核谤ICH指导原则Q11原料药的开发和生产(化学实体和生物技术生物实体)矮觉布常彝信陪鳞阔鲍凄列鹊裂范鼻毅臼炳瓢铺欣嫁富圭集丽纠笋吼易眼榔蓬峻乔乞奴药符隘簧怎苞舰尾豌件瘸憎的辗恩怯竟米私砚磺桃孔吕古损圃棉饭衍弗湖煌签疟娜盂坛闷耪再伴硅钻雾廊虏梅典各酌膝庸著鸭蛾袒哇毕斡描戒惟这邓查钝蒲宣狱啸资售坛买皋轴炼钵混脊吓蛊泉檀楔情褪向伯跨购浩形房骆拴视贺腹百酶铂渤政虏赚勒毖碉乾耘艇啃闯凡身店积腑节懦一驮霜逆履属拴凝淘崇泻挪棕互弧命卿奶金选怂坦捣床路离烹抠驼匹型了逾见匹鼠抬猜苹辫末痞肉陵槛烷魂反昂克债壬且蔡亭碧碾佩阅巡河赊俭蛆玉交宰雅颅猫牲布液瓜固驾啦概名淬窄球碎迄之洪娱坪寐悉嫂巳沏忆渴有GMPMay2011EMA/CHMP/ICH/425213/2011ICH/Committeeformedicinalproductsforhumanuse(CHMP)ICHguidelineQ11ondevelopmentandmanufactureofdrugsubstances(chemicalentitiesandbiotechnological/biologicalentities)ICH指导原则Q11原料药的开发和生产(化学实体和生物技术/生物实体)Step3翻译/审核:谢永/ChankTransmissiontoCHMPAdoptionbyCHMPforreleaseforconsultationEndofconsultationn(deadlineforcomments)May2011May2011September2011CommentsShouldbeprovidedusingthistemplate.TheCompletedcommentsformshouldbesenttoICH@ema.europa.eu7WestferryCircus●CanaryWharf●LondonE144HB●UnitedKingdomTelephone+44(0)2074188400Facsimile+44(0)2074188416E-mailich@ema.europa.euWebsite©EuropeanMedicinesAgency,2011.Reproductionisauthorisedprovidedthesourceisacknowledged.ICHguidelineQ11ondevelopmentandmanufactureofdrugsubstances(chemicalentitiesandbiotechnological/biologicalentities)TABLEOFCONTENTS目录1.INTRODUCTION介绍.................................................................................................................42.SCOPE范围...............................................................................................................................................43.MANUFACTURINGPROCESSDEVELOPMENT制造工艺开发....................................................................53.1.GeneralPrinciples总则...................................................................................................................................................53.1.1.DrugSubstanceQualityLinktoDrugProduct将原料药质量与制剂药品联系起来..............53.1.2.ProcessDevelopmentTools工艺开发工具...........................................................................53.1.3.ApproachestoDevelopment开发的方法.............................................................................63.1.4.DrugSubstanceCriticalQualityAttributes原料药的关键质量属性(CQA)....................73.1.5.LinkingMaterialAttributesandProcessParameterstoDrugSubstanceCQAs将物料属性和工艺参数与原料药的关键质量属性相关联..............................................................................................83.1.6.DesignSpace设计空间.......................................................................................................93.2.SubmissionofManufacturingProcessDevelopmentInformation制造工艺开发信息的注册递交.........103.2.1.OverallProcessDevelopmentSummary全面的工艺开发总结.........................................103.2.2.DrugSubstanceCQAs原料药的CQAs.................................................................................113.2.3.ManufacturingProcessHistory制造工艺历史......................................................................113.2.4.ManufacturingDevelopmentalStudies制造开发研究...........................................................124.DESCRIPTIONOFMANUFACTURINGPROCESSANDPROCESSCONTROLS制造工艺描述和工艺控制.125.SELECTIONOFSTARTINGMATERIALSANDSOURCEMATERIALS起始物料和源物料的选择.......135.1.GeneralPrinciples通则.................................................................................................................................................135.1.1.SelectionofStartingMaterialsforSyntheticDrugSubstances化学合成原料药的起始物料的选择.......................................................................................................................135.1.2.SelectionofStartingMaterialsforSemi-syntheticDrugSubstances半合成原料药的起始物料的选择.....................................................................................................................................................145.1.3.SelectionofSourceMaterialsforBiotechnological/BiologicalProducts生物产品的起始物料的选择.................................................................................................................................................................155.2.SubmissionofInformationforStartingMaterialorSourceMaterial起始物料或源物料的信息申报.....155.2.1.JustificationofStartingMaterialSelectionforSyntheticDrugSubstances合成原料药的起始物料的选择的合理解释.................................................................................................................................155.2.2.JustificationofStartingMaterialSelectionforSemi-SyntheticDrugSubstances半合成原料药的起2/37ICHguidelineQ11ondevelopmentandmanufactureofd