1、1Objectives 培训目的oIntroduction to GMPs?o良好生产操作规范（GMPs) 概述oWhy do we need GMPso我们为什么需要GMPs？oWhen to we use GMPs?o我们何时需要用到GMPs？oGeneral Overview of basic cGMP RequirementsoCGMP基本要求总揽oKey differences from the QMSo与质量管理体系的关键区别oImplementing for successo成功的方法2Introduction to GMPs 良好生产操作规范引言a.GMPs defined b
2、.History c.Applications d.GMPs 定义e.历史f.适用范围3cGMPs Overview最新食品及药物生产质量管理规范概要North Asia Quality Managers MeetingMarch 6, 2007Taipei Taiwan 北亚质量经理会议 2007，3，6，台北，台湾4Current Good Manufacturing Practices (cGMP) 最新食品及药物生产质量管理规范Good Manufacturing Practices are.the current minimum guidelines for controlling
3、the manufacturing, processing, packing and holding of drug products to assure that the products are safe for use, are properly identified, of proper strength, and of appropriate quantity and quality.生产管理规范是指。现行是指用以控制生产，进程，包装和保持药品的最小方针，以此确保产品固有的数量及质量，并安全的被使用。5GMP History GMP历史Food and Drug Administra
4、tion - Federal Food, Drug and Cosmetic Act of 1938, as Amended: 1938年美国联邦政府食品药物管理规范规定：To protect the consumers from unsafe or deceptively labeled or packaged products by prohibiting the movement in interstate commerce of adulterated or misbranded food, drug, devices and cosmetics.通过禁止次级或被错误标记的食品，药品，
5、设备和化妆品国际贸易中的变动，以确保消费者的利益不被危险性的或者带有欺骗性的标签和包装的产品所侵害。6Food and Drug Administration 食品，药品规程The U.S. Food and Drug Administration (FDA) is a public health agency that is charged with protecting American consumers by enforcing the U.S. Federal Food, Drug, and Cosmetic Act and other related public health l
6、aws. 美国食品药物管理局是通过实施美国联邦政府食品药物管制及其他相关公众健康法规，以确保美国消费者健康的公众机构。7Food and Drug Administration 食品和药物管制Basic FDA Product RequirementsSafe for intended useDrugs and devices effective for intended useNot adulterated (i.e., contains what, and only what, it is supposed to contain)Not misbranded (i.e., labeled
7、as it should be)Manufactured in compliance with applicable cGMPs美国联邦政府食品药物管制基本要求产品用途安全性药品及设备有效使用未渗入次品（如产品包含成分，仅有成分等）无错误标记（如标签）按照可行的最新食品及药品生产质量规范进行生产8Why do we need GMPs 我们为何需要药品生产管理规范？a.Where is K-C going?b.Liabilityc.Compliance (FDA audits and reports)d.KC在哪些方面实施？e.职责f.承诺 (美国联邦政府食品药物管理局审核和报告）9K-C D
8、irection K-C引言“A host of internal and external challenges are driving significant change within Kimberly-Clark. Therefore, we are making changes to become a winning global health and hygiene company.” (taken from the K-C Intranet GBP site) 一系列内外部的挑战正随着金伯利发生着强大的变化。因此，我们正在朝着全球领先的健康卫生产品公司而努力着。（摘自KC企业内部
9、GBP网）10K-C Expectations KC的期望Corporate Integrity and ExpectationsProduct Safety ClearancesMeets Customer RequirementsOnly Approved MaterialsProperly and Effectively PackagedAccurately Branded and LabeledCorporate Manufacturing StandardsEnsure inspection readiness企业诚信和展望产品安全性满足客户要求仅被认可的材料合理有效的包装精确的商标
10、及标识企业生产标准安全监查预备11Why cGMPs？为何实施cGMPs?oIts good businessoProtect our consumersoProtect our businessoCustomer requirementsoMaintain regulatory complianceoRules for producing Safe and Clean ProductsoPart of an appropriate Quality Systemo良好的商机o保护我们消费者的利益o保护我们的商业机会o客户要求o遵守规范的承诺o产品安全性和整洁度的规范o适当的质量体系12GMPs
11、 are part of an “Appropriate” Quality System GMPs是特有的质量体系The Kimberly-Clark Quality Management System requirements (QMS) includes all regulatory requirements for a “appropriate” quality system.ISO 13485 includes all regulatory requirements for a “appropriate” quality system.ISO 9001 does not include
12、 all GMP requirements金伯利质量管理体协要求指所有针对特有的质量体系而调整的要求ISO13485指所有针对特有的质量体系而调整的要求ISO 9001不包含所有的GMP要求13Legal Responsibilities 法律责任oMust comply with the Federal Food, Device, Drug, and Cosmetic ActoMust comply with the Fair Packaging and Labeling ActoMust comply with Regulations issued under the authority
13、of these Laws oEnforced as part of the FD&C Acto必须遵照美国联邦政府食品，设备药物管制规程o必须遵照美国公平包装标式法o必须遵照由上述权威法律所签署的相关规章o必须实施美国联邦政府食品药物管制规程14When would we use GMPs? 何时使用GMPs？a.Production of regulated productsb.Customer requirementsc.Business requirementsd.Protect the brand or businesse.Protect our C/S/C/U. f.符合规则的产品
14、生产g.客户要求h.商业要求i.保护品牌和商业j.保护我们的 C/S/C/U15Also known as 21 CFR 820, Part 820, cGMPApplies to all medical device firmsMost Class 1 devices are exempt from design controlsSome very low risk Class 1 devices are exempt from all except complaint handling and record keeping requirements作为最新食物药品生产质量规范章程，章节82
15、0适用所有医疗产品商绝大多数级别一的产品免除设计方面的控制一些风险较小的级别一的产品可免除除了处理投诉和保持记录以外的其他要求FDA Quality System Regulation 美国联邦政府质量体系规章16Medical Device cGMPs 医疗设备动态药品生产管理规范Medical Device Classes:医疗设备等级Class I 等级Class I devices are subject to the least regulatory control. They present minimal potential for harm to the user and ar
16、e often simpler in design than Class II or Class III devices. Class I devices are subject to General Controls as are Class II and Class III devices.一级别的产品受调整的控制，并相对于级别二和三而言，在设计上较为简单但对使用者几乎没有任何的伤害。一级别的产品在常规控制中和级别二三相同。Examples of Class I devices:Unscented Pads or LinersExamination glovesAdult incontin
17、ence exempt一级别产品引例：无气味的衬垫测试手套Note:Most Class I devices are exempt from the premarket notification and/or good manufacturing practices regulation.注意：大多数一级品除了先期市场告知外，都必须遵守良好的生产实践定律。17Medical Device cGMPs 医疗产品的最新生产质量操作规范Class II 等级IIClass II devices are those for which general controls alone are insuff
18、icient to assure safety and effectiveness, and existing methods are available to provide such assurances. In addition to complying with general controls, Class II devices are also subject to special controls. 二级别的产品是指那些在一般控制下还未足够保证安全性能及效果的情况下，并存有其他技术以更好的确保其安全性，除一般控制之外，二级别的产品还受控于特殊控制。Examples of Clas
19、s II devices:二级别产品举例：Surgical drapes 外科医用台布Tampons 止血棉塞18Medical Device cGMPs 医疗产品的cGMPsClass III 等级IIIClass III is the most stringent regulatory category for devices. Class III devices are those for which insufficient information exists to assure safety and effectiveness solely through general or s
20、pecial controls.级别三是最严格的级别，三级别的产品是指除了一般和特殊控制外，还未有足够的信息以确认产品的安全性的产品。Class III devices are usually those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury. 级别三的产品通常是那些用以支持和维护人
21、类生活，并避免发生人体伤害或潜在及不合理的伤害风险的具有实质重要性的产品。Example of Class III device: 级别三的产品举例：implantable pacemaker 植入式心脏起博器 19Medical Device Reporting (21CFR 803)Corrections, Removals and Withdrawals (21CFR 806)Labeling (21CFR 801) Electronic Records, Electronic Signatures (21CFR 11)Registration & Listing (21CFR 807)
22、Quality System Regulation (21 CFR 820) with exemptions医疗产品报告更正，解除标注电子记录，电子签名登记和名录质量体协规章（含免除部分）What FDA Regulations Apply? 美国联邦政府食品药物管理规定适用什么？20CE Marking - Medical Device Directive (MDD 93/42/EEC) if the product is distributed in the European UnionlDevices must meet the essential requirements in Ann
23、ex I.lTechnical documentation is required as outlined in Annex VIIlCE mark is affixed to the product in accordance with the procedure described in Annex XII.lCE标记-医疗产品指导，若该产品分售到欧洲联盟l产品必须符合必须的要求（见附录I）l技术文档要求在附录VII概述lCE标记必须按照附录XII中描述的进程贴上What Other Quality System Standards Apply?其他质量体系标准适用什么？21Cosmeti
24、c Products 美容用品“Articles, other than soap, intended to be rubbed, sprinkled, or sprayed on, introduced into or otherwise applied to the body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance without affecting the bodys structure or function.”那些除了肥皂外
25、用于使身体清洁美观等的任何喷雾或洗涤用品，并对身体不造成任何的伤害。cGMPs Cosmetic Products美容用品的生产质量操作规范cGMPs - ONLY a guidelineManufacturer responsible for safety of product (ie not adulterated, misbranded)No drug claims (implicit or explicit) can be made“KC GMPs” apply to manufacturing, storage and distribution of product最新生产质量操作规
26、范-仅是个方针生产者必须对产品的安全性负责（如不可有次品）无任何有毒物质金伯利的生产质量操作规范适用于产品的制作，储存，分销FDA Facility RegistrationCosmetic Products 美国联邦政府美容用品注册None required by statuteVOLUNTARY registration allowed (21CFR 710)Registration of each manufacturing and packaging facilityIdentify company name, address and product name in registrat
27、ion法规未要求的自行的注册每个生产及包装设备的注册公司名称，地址和产品名称的注册Definition of Adulterated Product 次品的定义Contains any poisonous or harmful substance which causes injury under recommended condition of useConsists in whole or part of filthMade under filthy conditionsContainer composed of harmful substance which gets into the
28、product含有任何有污染或有害的在产品使用状况下可引起伤害的物质有部分或完全污物在有污物情况下生产的集装箱有能造成产品损害物质的Definition of Misbranded Product 错误标记产品的定义False and misleading labelingFailure to label w/name and address of mfg., pkg., or distributorLacks net content statementNoncompliance of required labelingNonconforming colors错误的标记标记上未印有重量和分销商
29、缺乏净含量未确认的颜色26Overview of GMPs GMPs总揽Medical Devices 医疗产品Cosmetics 美容产品27cGMPs for Medical Devices医疗产品的最新生产操作规范A. General Provisions 一般规定B. Quality System Requirements 质量体系要求C. Design Controls 设计控制D. Document Controls 文档控制E. Purchasing Controls 采购控制F. Identification and Traceability 验明和可追述性G. Product
30、ion and Process Controls 产品及进程控制H. Acceptance Activities 可接受性I. Nonconforming Product 非确认产品J. Corrective and Preventive Action 纠正及预防措施K. Labeling and Packaging Control 标签和包装控制L. Handling, Storage, Distribution, and Installation 处理，储藏，分销和安装M. Records 记录N. Servicing 服务O. Statistical Techniques 技术28GMP
31、 Linkage to the QMS 生产操作规范和质量管理体系的联系a.What are the similar requirements?b.What are the key differences?c.What is the impact of the required changes?d.要求的相似处？e.关键差别？f.要求变化的作用？29QMS/GMP Similarities 质量管理体系和生产操作规范的相似处The QMS was written to work in harmony with external standards and global formats. The
32、 QMS high level requirements fit within the specifics of regulatory requirements.质量管理体系是作用于符合外部和全球性的标准质量管理体系高级别的要求必须符合可调整的要求之内30Specific requirements for GMPs GMPs的特殊要求Complaints ProcessDesign Verification & ValidationDevice Master Record (DMR)Device History Record (DHR)Quality System RegulationElec
33、tronic RecordsProcess ValidationChange ControlsRegistrations and ApprovalsOthers投诉方法设计认可和确认产品主要记录产品历史记录质量体系规章电子记录方法确认改变控制登记和认可其他31Any written, electronic or oral communication that alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness or performance of
34、 a device after it is released for distribution.任何落笔的，电子的或口头交流的关于在产品出产或分销后，对产品的说明，质量，耐久性，可靠和安全性的不完备的申诉。What is a Complaint?什么是投诉32Requirements are discussed in 21CFR 820.198 要求在21CFR 820.198被讨论过The regulation requires 规章要求lDocumented procedures 进程文档记录lTimely and uniform processing 及时一致的处理lProcess fo
35、r evaluation/investigation 评估方法lAdverse event consideration (serious injury or death)不利方面的考虑（严重的损伤或死亡）Additional requirements apply to complaints alleging serious injury or death (21 CFR 803)正对严重损伤或死亡的申诉的额外要求（21CFR803)What About Complaint Files? 投诉文件33A compilation of records containing the producti
36、on history of a finished device. 记录需包含每个成品的生产历史A DHR includes DHR包含 lDates of manufacture 生产日期lQuantity manufactured and released 数量和生产lAcceptance records 可接受记录lPrimary identification label 主要确认标记lDevice identification and lot number 产品确认和生产标号What is a DHR?DHR是什么？34Maintained at the manufacturing si
37、te or otherwise reasonable accessible.维护生产地或合理进入Legible and complete (errors must be appropriately corrected) 易读的和完成的（错误必须适当纠正）Retained for the life of the product (minimum 2 years from date of release).产品寿命需维持从生产日期起至少2年）Exceptions include Management Review, Quality Audits and Supplier Audits.特殊情况包含
38、管理检阅，质量审核和供应商审核Record Requirements 记录要求35Additional requirementslElectronically stored must be backed uplElectronically created must comply with Part 11 requirementslElectronically signed must comply with Part 11 requirementslCSV Roadmap http:/ Record Requirements 电子记录要求36Design Verification and Val
39、idation, Process Validation 设计及方法确认和批准Design Verification and ValidationslMust verify design “Output” meets “Input”.lMust validate design under normal operating conditions with production product. lDesign validation must Risk assessments.l设计的确认和批准l必须确认设计从生产和出产的一致l必须在常规产品生产操作的情况下批准设计l设计批准必须经过风险评估Proc
40、ess Validations 方法批准lWhere results of a process can not be verified, a process shall be validated, i.e., bioburden, cleaning, sanitization, etc. 当一种方法的结果不被查证时，37Change Requirements 改动要求Change control process for the identification, documentation, validation, or where appropriate verification, review
41、 and approval of changes before implementation. 改变控制进程是在改变实施之前，针对改变的，审阅，查证，认可随后做出相应的审批，法律批文和文档的过程。These changes include, but are not limited to: 这些改变包含以下方面但不仅限于此：Design 设计Process 进程Software 软件Cleaning 清洁Sanitization 清除干净38GMP Controls - What needs to be in place? 什么适当的方面需要GMP控制Understand the scope,
42、risk and regulationsAssess risks HACCPProduct History领会范围，风险及规章评估风险-HACCP 危害分析关键控制点产品历史39Risk Assessment Scope 风险评估范围40How do we assess GMP risks?我们如何评估GMP风险？HACCP is a proactive systematic approach to the identification, assessment of risk and severity, and control of biological, chemical, and phys
43、ical hazards/contamination associated with a product, production process or practice. HACCP是一种较有体系的方法，使产品在生产实践过程中，对产品生物化学物理技能等方面的风险及严肃性的审查及评估。 41 Why use HACCP?为何适用危害分析关键控制点Its all about making Safe and Clean products and meeting Good Manufacturing Practices! 一切都是为了生产安全整洁的产品Regulatory requirements 调
44、整要求Competitive advantage for identification of design issues early 设计版本及早的确认具有竞争性的优势Protection for product liability awards 产品审查责任的保护Learn about HACCP as a tool for assessing contamination risks 学习HACCP作为评价混淆风险的工具HACCP for Diapers - Example43GMP Next Steps GMP下阶段Impact on North AsialKorealChinalTaiw
45、anl对北亚的影响l韩国l中国l台湾Plans for implementation 计划实施Training 培训Project Management 项目管理44The 3 Keys to Success with GMPs GMPs成功的三点关键1.Critical Start Infrastructure and Systems2.Avoid Surprises Communicate and plan Early3.Product Design, Development, Process and Approvals4.开始评论-构造和体系5.避免意外事件-及早沟通与计划6.产品-设计
46、，发展进程和认可45Resources 资源GRSAlRegulatory AffairslCART (Compliance and Resource Team)lGlobal Capability TeamslBusiness Quality Leadersl规程lCART（资源团队）l全球力量团队l商业质量领导46Questions 问题47Appendix A 附录ACosmetic and Drug GMPs美容及药品生产质量操作规范48Cosmetic / Drug GMPs 美容及医药生产质量操作管理规范Buildings and Facilities 生产场地及设备lBuildi
47、ngs used in the manufacture or storage of cosmetics are of suitable size, design and construction to permit unobstructed placement of equipment, orderly storage of materials, sanitary operation, and proper cleaning and maintenance. lFloors, walls and ceilings are constructed of smooth, easily cleana
48、ble surfaces and are kept clean and in good repair. lFixtures, ducts and pipes are installed in such a manner that drip or condensate does not contaminate cosmetic materials, utensils, cosmetic contact surfaces of equipment, or finished products in bulk. l生产场地是指用于合适尺寸，设计的美容产品的生产和储存，并用于设备的堆放，日常原料的储存，
49、卫生的操作以及适度的清洁和维护。l地板，墙壁和天花板必须平整的建筑，并较易的可做表面清洁和良好的维修。l装置物，电线以及管道等必须被合理安装，以避免有房屋渗漏现象导致机械表面，箩筐里面的成品的破损。49Cosmetic / Drug GMPs美容及医药生产质量操作管理规范Buildings and Facilities (continued)lLighting and ventilation are sufficient for the intended operation and comfort of personnel. lWater supply, washing and toilet
50、facilities, floor drainage and sewage system are adequate for sanitary operation and cleaning of facilities, equipment and utensils, as well as to satisfy employee needs and facilitate personal cleanliness. l照明以及通风必须足以使个人舒适和适应操作l水供给，洗手间设备，地面排水渠道和排污系统必须足以满足卫生操作和设备清洁也必须满足雇员个人的清洁50Cosmetic / Drug GMPs美
