De-mystifying GMP解疑GMP

1、GMP502.1,De-mystifying GMP 解疑GMP Dr Bob Pietrowski Bob Pietrowski 博士 David Begg Associates,疙澜幌吨撒隙烤殷盖姆银错捆到揪鬃纽帛黑蓑嫁谨耳岩盖碍幸阑腾佣金附De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.2,De-mystifying GMP解疑GMP,Introduction 介绍 Quality Assurance, GMP and Quality Control 质量保证，GMP与质量控制 What is GMP ? 什么是GMP ? Lega

2、l Status of GMP GMP的法律地位 GMP : The Industry and the Regulators GMP：行业与法规制定者 Essential Elements of GMP： GMP的基本元素 Summary 摘要 Essential Messages 基本信息,滩耕耳毡障殖烙旷亦查桑铅戮蚕扫厌泛篓棚削严划贴鸣统雷弄赤前灭邮篷De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.3,MORAL and LEGAL Obligations of Manufacturers制造商的道德与法律责任,To organize

3、 their activities so that 规范业界的行为以使得 Products are FIT FOR INTENDED USE 产品符合指定的用途 Comply with REGULATORY COMMITMENTS 遵守对法规的承诺 Patients not at risk because of inadequate: 防止由于以下的不当，使患者处于风险中: SAFETY安全 QUALITY质量 EFFICACY功效,屎桩辰兢赢债退揭鞋紊使丢逢媚晋迸帐檬樟疑涯四耳债宣拌双菲歹旨玄所De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP5

4、02.4,EU Guide to GMP .欧盟关于GMP的指南,ATTAINMENT of QUALITY OBJECTIVE 达到质量目标 Is responsibility of SENIOR MANAGEMENT 是高层管理者的责任 Requires PARTICIPATION and COMMITMENT by : 要求下列人员的共同参与及承诺: Staff in many Departments and at all levels多数的部门和各个级别的员工 The Companys Suppliers公司的供应商 The Companys Distributors公司的销售商,从芳

5、瞩峭嚎羌崎斩蚜颇蘸田憨激恐瑞绥很无拂吭拿聂蚜宙峦辆梆衙彬钦赤De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.5,To Achieve the Quality RELIABLY there must be a .要达到质量可靠性，必须有.,COMPREHENSIVELY DESIGNED and CORRECTLY IMPLEMENTED system of QUALITY MANAGEMENT incorporating . 全面设计的与正确实施的质量管理系统, 它综合了 QUALITY ASSURANCE 质量保证 GOOD MANUF

6、ACTURING PRACTICE良好操作规范（或称:生产质量管理规范） QUALITY CONTROL质量控制,嚏软慕貌盾酌瘟济狐曹串烂蜕夏染筋溜书虎堰汉检架诚册荣锰浦椒波莫丘De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.6,Quality Assurance .质量保证.,The CREATION and OPERATION of : 建立并实施: STANDARDS 标准 PROCEDURES 过程 MANAGEMENT SYSTEMS管理系统 To GUARANTEE the QUALITY of a PRODUCT throu

7、ghout its “LIFE CYCLE ” 保证产品在整个“生命期” 的质量,槐征擞掣灯攫奄鲍浇进体烬酣沥臻栋颂漠税醒锹猫充玩符痛无嫡邀寿触宦De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.7,低沃丰糕举调淋廊躇叹岭瘫兵窃嘘猴漠爆芦焦房经胆社蓟澜褐牙呜鸥赤幼De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.8,ALL FACTORS. inside and outside the factory 工厂内部的与外部的所有的因素. BEFORE, DURING AND AFTER MA

8、NUFACTURE 在生产之前，生产期间和生产之后,浇澜呛贮仁但雷丙拣挂葵区尖倔屁缎岭项士叮饺隧龄员抛指谅纺掏尊渊酪De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.9,Good Manufacturing Practice 良好操作规范,Part of Quality Assurance aimedat ensuring that products are CONSISTENTLY MANUFACTURED to the REQUIRED QUALITY within the FACTORY 质量保证的一个目的是确保工厂按照要求的质量始终

9、如一地生产合格的产品。,痕售隙稽说跟鸿呢铣浸调敞乔巢胶锤鞍祈步烤稽拼斗贷着淬腿懒曝懊但汕De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.10,躇摘糕磐孝摊掘章籍给度馁未禾虎钒桨创肌突臆愉谈邹蔬昌糟亨亮浸璃鸽De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.11,Tests, inspections and measurements carried out on SAMPLES taken before, during and after MANUFACTURING and PACKAG

10、ING to provide evidence that a starting material or a finished product will or will not meet its WRITTEN SPECIFICATION 对生产与包装之前，期间和之后的样品进行测试、检验与测量，以提供原始材料或最终产品是否能够符合书面技术规范的证据。,Quality Control. Part of GMP质量控制.GMP的一部分,言胁湾布亏惭烹友钢汹沾很允嘻淑异联影领狰汝渠涉递令向贺眼槐唤蜘容De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502

11、.12,Quality Control is Concerned With 质量控制涉及,Sampling programmes 采样程序 Specifications 规范 Testing 检测 PHYSICAL CHEMICAL BIOLOGICAL 物理的、化学的与生物方面的测试 Documentation 文件 Standards 标准 Release procedures 放行程序 and GOOD CONTROL LABORATORY PRACTICE 及良好的实验室控制规范,补成渝踩审庄裙装画酿铸硼购液能紫尔耘输弯蚊古轻埃帆绊顷狮谭粉译轧De-mystifying GMP解疑GM

12、PDe-mystifying GMP解疑GMP,GMP502.13,游稗节淖侩弛委怪吼称砂漳伙是努饮路毛拭酥侨离甩街鬃劲滔惧跑拘摘埠De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.14,What is GMP ? GMP 是什么？,梗好济既碉膳海洽蔫墒谁泪乃津辱祷鹊键遥却辞阁卑煤挥俩乓元戎荫彼心De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.15,GMP stems from recognition that QUALITY can be of TWO types .GMP起源于认识

13、到质量可以分为两种类型.,INTRINSIC 内在的 inherent suitability of active in a particular formulation 特定配方中的有效成分固有的适宜性 safety and efficacy of the formulated product when made correctly and used as indicated 正确制造并按规定使用的配方产品的安全性与功效性 EXTRINSIC 外在的 suitability of any batch of a manufactured product 任何生产批次产品的适合性 quality

14、 determined by the manufacturing practices 由操作规范决定的质量,勾睹初帘捻铰汗诱结妖柄郡晋煎某吭搏阳泼始耪铁缄甲勃荷妇浇鞋碑氢式De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.16,Extrinsic Quality depends on :外在质量依赖于：,Quality of starting materials 原材料的质量 Quality of Premises and Plant 工厂设施及其环境的质量 Suitability of the Process 过程的适宜性 Absence

15、 of Processing Problems 没有加工生产问题 Quality of In-Process Controls 过程控制的质量 Training and Attitude of People 人员的培训与态度 . in short GMP GMP简而言之,狸划痢作庇峦故陶慑是拯界嫌彩窖孙悠庞冒锭郴类荫裁劳皿惫舅略爵照尚De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.17,GMP is concerned with .GMP涉及.,All activities .所有的活动 Delivery of materials a R

16、elease of products 原料的运送a 产品的放行 All processes .所有的过程 Logistics a Manufacturing Packaging 物流a 加工包装 Quality Control .质量控制 Materials a In-process a Finished Products 原料a加工a成品 Good Management .良好的管理 People a Data a Communications 人员a 数据a 沟通,碉楔垃杭滴晶缉寒吞惭墨黄牟泌涸格氓抵唉御棘述省勘邢跨框尧湃嵌奢百De-mystifying GMP解疑GMPDe-mystif

17、ying GMP解疑GMP,GMP502.18,Principles of GMP .GMP 的原理.,People人员 Premises场地 Products产品 Processes过程 Procedures程序,盒乒这滇谦放僚拖芯虚堤萝翻必棉秽厂莎连公句痘侍钳栓览逊蚂冰岔试根De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.19,The Legal Status of GMP GMP的法律地位,寺危藤断渡蓟杂闪枝千讥桐即考剁愤蕊封渴凄岿斋港乏找狱益草揉绦蛤狡De-mystifying GMP解疑GMPDe-mystifying GMP解

18、疑GMP,GMP502.20,Legally binding regulations in USA 在美国，是法律意义上的规章 Updated annually - hence “current” 年度更新 - 因此标明为“动态”,GMP has been LAW since 1962 从1962年开始，GMP已经立法,“Current” Good Manufacturing PracticeRegulations (cGMPs) detailed inCODE of FEDERAL REGULATIONS (Title 21 - Food and Drugs - Parts 210 and

19、211) 在联邦法规中对动态良好操作规范cGMPs的规章作了详细描述 （标题21-食品与药品-210与211部分）,Legal Status of GMP in USA .GMP在美国的法律地位,澈孺唤导嗅梳翌叼掀闻痹误菇绣嚎所帕妊鱼确驼炔身坟痕舵叔涸腻谬萌毕De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.21,GMPs mean the requirements found in the respective legislations, regulations, and administrative provisions for met

20、hods to be used in, and the facilities or controls to be used for, the manufacturing, processing, packing, and/or holding of a drug to assure that such drug meets the requirements as to safety, and has the identity and strength, and meets the quality and purity characteristics that it purports or is

21、 represented to possess GMPs是指在法律、法规与行政规定中对制造、加工、包装和/或扣留药品的过程所使用的方法、使用的设施或控制措施的要求，以确保药品的安全性，并具有识别特性与浓度，符合其声称或描述的质量与纯度的特性 。,GMP -Good Manufacturing PracticeGMP- 良好操作规范,21 CFR 210.1(a) 21-联邦法规- 210.1(a),萧玲佑匡翠囤牢挨丘雪支亲调说乙铆茎盾贪烃仑性矮亏巧蚜锑佩拣汽冶仲De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.22,Legal Status

22、 of GMP in USA .GMP在美国的法律地位.,Regulations cover . 法规包含. ORGANISATION and PERSONNEL组织与人员 BUILDINGS and FACILITIES建筑物与工厂设施 EQUIPMENT设备 CONTROL of Components, Drug Product Containers and Closures 组分，药物产品容器与密封的控制 PRODUCTION and PROCESS CONTROLS生产与过程的控制 PACKAGING and LABELLING CONTROLS包装与标签的控制 HOLDING and

23、 DISTRIBUTION保留与配送 LABORATORY CONTROLS实验室控制 RECORDS and REPORTS记录与报告 RETURNED and SALVAGED DRUG PRODUCTS退回和剩余产品,租缎岗炸我释罩股车螺耳混厂鞍杠途努孵殊枯拴汁畴鳃莽踊帜饯谅镰汝噎De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.23,Directives . THE LAWGMP Guidelines . INTERPRETATION 指示 . GMP导则的法律 .解释,Legal Status of GMP in EU.GMP在欧

24、盟的法律地位,1970sEuropean Countries publish GMP guides 20世纪70年代 欧洲国家出版了GMP导则 First EC Guide to GMP 1989 第一部欧盟的GMP导则 Compliance with GMP made compulsory in all member states 1992 所有成员国内符合GMP的强制性要求 Compliance with GMP extended to cover IMPs 2004 GMP要求扩展到IMP（工业管理程序）上,暴晤陋竿铬棍烂华吸迄缉赔酥旗得郊融佛九闲币泅渡磐哗别吴基脓掉牌金De-mysti

25、fying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.24,That part of QUALITY ASSURANCE which ensures that products are consistently produced and controlled to the quality standards appropriate to their INTENDED USE 是质量保证的一部分，目的是确保产品按照与用途相适应的质量标准稳定进行生产和控制的 EU Volume IV of the Rules“Good Manufacturing Practice

26、 for Medicinal Products” 欧盟规则的IV卷 药品良好操作规范,GMP . Good Manufacturing PracticeGMP .良好操作规范,眼丘圆餐曝歼妻峪勉彬邦宪暴铲泄涤甚逊捍碌愧妓这禹嗜赖蔫茫邀许喘式De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.25,Legal Status of GMP in EU.GMP在欧盟的法律地位,GMP Guidelines . interpretation of GMP directives GMP指导方针.GMP指导的解释 QUALITY MANAGEMENT质量

27、管理 PERSONNEL人员 PREMISES and EQUIPMENT场地与设备 DOCUMENTATION文件 PRODUCTION生产 QUALITY CONTROL质量控制 WORK CONTRACTED OUT工作的外包 COMPLAINTS and PRODUCT RECALL投诉与产品召回 SELF-INSPECTION自检 + Annexes on specialised topics +专题的附件,迄检肥棠阀躁密殴豹扭叫坯椒冀呼踪风径存伙巨摄舷瘤朋疑咏磨琅满等唇De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.26,EU

28、 and US GMP Requirements？欧盟与美国GMP的要求？,Underlying PRINCIPLES and PHILOSOPHY of GMP are similar . and especially concerned with GMP的根本原理与指导思想是相似的.特别是涉及 PEOPLE人员 PREMISES场地 PROCESSES过程 PRODUCTS产品 PROCEDURES程序,狭侦玖锨秧支桩袒娄水嗡警席陆焊濒革藉异钱晃镰拦步僧苏虫靠祖按油地De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.27,GMP . t

29、he way in which appropriate product quality is reliably achieved ! GMP .实现产品质量可靠的方法 THERE is NOTHING MYSTERIOUSabout GMP ! 关于GMP，没有任何神秘的事情! Nor is it simply the figment of the imagination of the REGULATORY AUTHORITIES 它也不是简单的法规部门凭空想象出来的,GMP . Industry and Regulators GMP . 行业与规范制定者,坛恃叫数缓射站区荐兵惫困剖劣铸闻毫砖

30、瑶甸雄谱涉壬瓶汤靳撬县嘱倡凹De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.28,It is a DISTILLATION of ACCEPTED GOOD PRACTICES agreed between Industry and Regulators 它是被行业与法规部门公认的可接受的良好操作的精髓,GMP . Industry and Regulators GMP . 行业与规范制定者,母霖轿淳喂辞损理瑶宗荷笨斡挤狈算群财虎揣钙屁斜往矾博得皑帆央夫灰De-mystifying GMP解疑GMPDe-mystifying GMP解疑G

31、MP,GMP502.29,etc,Perusal of GMP Guidelines .GMP导则的精读.,Nothing which responsible manufacturers do not 负责任的制造商不能 agree with不同意 strive to comply with - in practice不在实践中努力遵守操作规范 Why should GMP INSPECTION sometimes turn into a PAINFUL and CATACLYSMIC event ? 为什么GMP检查有时会成为一次痛苦的和非常大的事件？,WHO 世界卫生组织,EU 欧盟,PI

32、CS 药品检查合作计划,FDA 食品药物管理局,麻斑修屎侯隆睦死负慌姻绑理澜垒春健装说住萎肘晃南煌瑞一略萎骸姑亿De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.30,Reason ?原因？,No difference in philosophy and principles of GMP . GMP的指导思想与原理上没有分歧. . BUT .但是 Difference in INTERPRETATION of HOW to achieve these principles in practice . and the WAY in whic

33、h manufacturers RESPOND 在实际中怎样实现这些原理的解释. 与制造者响应的方式存在差异,魄猩息念喻馏尹淖夏搀囤嵌过副肪恿搐那烤栋筛反债付确办星菌阎冯欣勺De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.31,The Secret of Success 成功的秘密 Getting the Basics Right 获得正确的认识,罐栓均找啮四窜俞熬拒掖序嫌冲挺乱怯以斋烃敲满编劈希闽你扭翼活叶纤De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.32,Essential

34、Elements of GMPGMP的基本元素,All manufacturing processes are : 所有制造过程应： Clearly defined 明确地定义 Systematically reviewed in the light of experience 依据经验，进行系统性的评审 Shown to be capable of consistently manufacturing medicinal products of the required quality and complying with their specifications 表明能够稳定地制造符合质量

35、要求与满足规格的医药产品 Critical steps of manufacturing processesand significant changes to the process are validated 制造过程的关键步骤与过程的重大变化应被确认,Basic requirements 基本要求,熄耶晓擂糜押岸鸵疮尸莆衔垄通厦喉津嚼栗密蹋痴荧艰蔽村校敖荒岁沽耀De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.33,Essential Elements of GMP GMP的基本元素,All necessary facilities

36、for GMP are provided, including : 提供有关GMP所有必需的设施，包括: Appropriately qualified and trained personnel 具有适当资格与受训的人员 Adequate premises and space 足够的场地与空间 Suitable equipment and services 合适的设备与服务 Correct materials, containers and labels 正确的材料，容器与标签 Approved procedures and instructions 批准的程序与指令 Suitable st

37、orage and transport 合适的储存与运输 Instructions and procedures are written in an instructional form in clear and unambiguous language, specifically applicable to the facilities provided 指令单上的指令与程序应是清楚、明确的语言书面叙述，特别是与之提供的设施相适应。,Basic requirements基本要求,醒幻妥册翅郎疾皱朋云果疡蕊聪踩马亩炉洞阔变函眩鸟卓宏身甜松析抡赊De-mystifying GMP解疑GMPDe-

38、mystifying GMP解疑GMP,GMP502.34,Essential Elements of GMP GMP的基本元素,Operators are trained to carry out procedures correctly 操作工应经培训，正确地按作业指导书进行操作。 Records are made, manually and/or by recording instruments, during manufacture which demonstrate that :在制造过程中，不论是用手工还是记录仪进行记录，它应能表明： All the steps required

39、by the defined procedures and instructions were in fact taken 按既定程序要求的所有步骤与指令已执行 The quantity and quality of the product was as expected 已达到预期的产品数量与质量 Any significant deviations are fully recorded and investigated 任何明显的偏离，已被完整的记录并进行调查,Basic requirements基本要求,官渊添屏渺狙锑辟焦匿多封嫩骆孪商池远慈当削拣敛耽蜡谴摈谜赖篇巾育De-mystify

40、ing GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.35,Essential Elements of GMP GMP的基本元素,Records of manufacture and distribution, which enable the complete history of a batch to be traced, are retained in a comprehensible and accessible form 生产和销售记录，应确保每批次都可追溯，并以易识别和易得到的方式保留 The distribution of products mini

41、mises any risk to their quality 产品的配送方式应使它们的质量风险减到最小 A system is available to recall any batch of product from sale or supply 有从销售或库存可召回任何一批产品的系统 Complaints about marketed products are examined, the causes of quality defects investigated and appropriate measures taken in respect of the defective pro

42、ducts and to prevent reoccurrence. 检查市场产品的投诉，调查质量缺陷的原因，对于缺陷产品采取适当的措施以预防再次发生,Basic requirements基本要求,鄂连戊闽盗辗纠豪檬浇允蜡陈恤遥悬笨嗽巍贺枢炽追法值撒米蹭煤逼摆豹De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.36,Specific Requirements for Quality Control质量控制的特殊要求,Samples are taken by methods and by personnel approved by QC 取样

43、方法和人员应经质量控制部门批准和授权。 Test methods are validated 测试方法应是有效的 Product assessment shall be performed, including a review and evaluation of relevant production documentation and an assessment of deviations from specified procedures 进行产品的评估，包括对相关生产文件的评估和评价，以及评估特定程序的偏离等。,宅笛虱吁兑写彤硕末丽勿蝴予匹安上井易皂择烫也睡啄脂嘴水抹也甚起狱De-my

44、stifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.37,Specific Requirements for Quality Control质量控制的特殊要求,No material shall be released for manufacture, or product released for supply, if it fails to meet its approved quality specification 如果不能满足经批准的质量要求，原料不准予用于生产，产品不能放行 Sufficient reference samples of S

45、tarting materials Products shall be retained to permit future examination if necessary 应当有足够的 原料 产品 的样品应当被保留，以便于将来可能的检查。,泳奄华尖分芳拽轰习丑逢卸砷体贰惑企荒寄答薪诗侄畴憎雌微汐馁盅控牟De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.38,Additionally 附加,Regular or rolling quality review of all products shall be conducted 必须对所有产品

46、进行日常的或滚动的质量评估 To verify 以验证 The consistency of the existing process已有过程的一致性 The appropriateness of current specifications 当前技术规范的适宜性 To highlight any trends 以显示可能的趋势 To identify the need for improvements to Products Processes 以识别对 产品与 过程改进的需要,痪态萧科卜掺粹黄索泄郁粗潮愉镭碌贤衍狞阿腻窖挣阻贾淹喂计矾壁班姿De-mystifying GMP解疑GMPDe-

47、mystifying GMP解疑GMP,GMP502.39,And Finally 最后,There shall be a procedure for Self- Inspection and/or Quality Audit to appraise the effectiveness relevance of the Quality Assurance System 必须建立评价质量保证体系有效性与适宜性的自检和/或质量审核的程序。,像摧逸鱼造童刨炔阀里妄乱肥谅掌榜万桐狭蔗谁泣漠沿硼六函晚雷氯酚窝De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP

48、502.40,SUMMARY 摘要,掳献卫亡让蚕宛歇蔼这圃棒邦谁恤德脾敏愈甘蛔籍胜弧俺需华吁吊蛆哨充De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.41,GMP is a natural consequence of the central role that PEOPLE and the PROCESS play in the achievementof QUALITY GMP是实现质量中两大要素：人员与过程的自然结果 It is GUIDELINES and GOOD PRACTICES developed via CONSULTAT

49、ION and CONSENSUS between MANUFACTURERS and REGULATORS GMP是通过咨询和制造商与法规制定者的共同意愿发展起来的导则与良好规范,Summary .摘要.,柠弗抒莆剁煞俱讹朵赞丽锰果蚕烛钎升筏伯粮涩湾诊鹃闯够伺速骆厢狮慕De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.42,Summary .摘要.,GMP seeks to minimise the VARIABLES which affect quality such as : GMP寻求影响质量的变数的最小化，如： Materials原料 Processes/methods of manufacture制造过程和加工方法 Equipment设备 Environment/Premises环境/场地 People人员,顿悄默息贿凹疯徘燃块删竟甲凭界戎壬强过糊赖祝颗零概趁绥曙估铲仆视De-mystifying GMP解疑GMPDe-mystifying GMP解疑GMP,GMP502.43,Summary .摘要.,These VARIABLES may be controlled by