《全球质量经理的培训教材》由会员分享，可在线阅读，更多相关《全球质量经理的培训教材（107页珍藏版）》请在金锄头文库上搜索。
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:Medical Device Classes:医疗设备等级医疗设备等级Class I Class I 等级等级Class I devices are subject to the least regulatory control. They present Class
16、I devices are subject to the least regulatory control. They present minimal potential for harm to the user and are often simpler in design than minimal potential for harm to the user and are often simpler in design than Class II or Class III devices. Class I devices are subject to General Controls C
17、lass II or Class III devices. Class I devices are subject to General Controls as are Class II and Class III devices.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。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 o
18、f Class I devices:Examples of Class I devices:Unscented Pads or LinersUnscented Pads or LinersExamination glovesExamination glovesAdult incontinence Adult incontinence exempt exempt一级别产品引例：一级别产品引例：无气味的衬垫无气味的衬垫测试手套测试手套Note:Most Class I devices are exempt from the premarket notification Note:Most Clas
19、s I devices are exempt from the premarket notification and/or good manufacturing practices regulation.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。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 等级等级IIClass II devices are those for
20、 which general controls alone are insufficient 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
21、，除一般控制之外，二级别的产品还受控于特殊控制。Examples of Class II devices:二级别产品举例：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 等级等级IIIClass III is the most stringent regulatory category for devices. Class III devices are those for which insufficient information exists to assure sa
22、fety and effectiveness solely through general or special 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, unreasona
23、ble risk of illness or injury. 级别三的产品通常是那些用以支持和维护人类生活，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：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, Electro
24、nic Signatures (21CFR 11)Registration & Listing (21CFR 807)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 Europea
25、n UnionlDevices must meet the essential requirements in Annex 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标记标记-医疗产品指导，若该产品分售到欧洲联盟医疗产品指导，若该产品分售到欧洲联盟l产品必须符合必须的要求（见附录产品必须符合必须的要求（见附录I）l技术文档要求
26、在附录技术文档要求在附录VII概述概述lCE标记必须按照附录标记必须按照附录XII中描述的进程贴上中描述的进程贴上What Other Quality System Standards Apply?其他质量体系标准适用什么？21Cosmetic 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, bea
27、utifying, promoting attractiveness, or altering the appearance without affecting the bodys structure or function.”那些除了肥皂外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 dru
28、g 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
29、710)Registration of each manufacturing and packaging facilityIdentify company name, address and product name in registration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 useC
30、onsists in whole or part of filthMade under filthy conditionsContainer composed of harmful substance which gets into the 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
31、., 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. Des
32、ign 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. Production 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. H
33、andling, 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 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
34、/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 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
35、ProcessDesign Verification & ValidationDevice Master Record (DMR)Device History Record (DHR)Quality System RegulationElectronic 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 tha
36、t alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness or performance of 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21
37、CFR 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 for 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
38、(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 production 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 identifica
39、tion 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 site 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 year
40、s 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 requirementslElectronicall
41、y signed must comply with Part 11 requirementslCSV Roadmap http:/ Record Requirements 电子记录要求电子记录要求36Design Verification and Validation, 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 w
42、ith 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Process 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 Requi
43、rements 改动要求Change control process for the identification, documentation, validation, or where appropriate verification, review 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Pr
44、ocess 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, 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?我们如何评估我们如何评估GMP风险？风险？HACCP
45、is a proactive systematic approach to the identification, assessment of risk and severity, and control of biological, chemical, and physical 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
46、危害分析关键控制点Its all about making Safe and Clean products and meeting Good Manufacturing Practices! 一切都是为一切都是为了生产安全整洁的产品了生产安全整洁的产品Regulatory requirements 调整要求调整要求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
47、责任产品审查责任的保护的保护Learn about HACCP as a tool for assessing contamination risks 学习学习HACCP作为评价混淆风险的工具作为评价混淆风险的工具43GMP Next Steps GMP下阶段Impact on North AsialKorealChinalTaiwanl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.Criti
48、cal 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，发展进程和认可45Resources 资源GRSAlRegulatory AffairslCART (Compliance and Resource Team)lGlobal Capability TeamslBusiness Quality Leadersl规程
49、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 生产场地及设备生产场地及设备lBuildings used in the manufacture or storage of cosmetics are of suitable size, design and construction to permit unobstructed place
50、ment of equipment, orderly storage of materials, sanitary operation, and proper cleaning and maintenance. lFloors, walls and ceilings are constructed of smooth, easily cleanable surfaces and are kept clean and in good repair. lFixtures, ducts and pipes are installed in such a manner that drip or con
51、densate 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，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
52、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 facilities, floor drainage and sewage system are adequate for sanitary operation and cleaning of facilities, equipment and ute
53、nsils, 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美容及医药生产质量操作管理规范Equipment 设备设备lEquipment and utensils used in processing, holding, transferring and filling are of appropriate d
54、esign, material and workmanship to prevent corrosion, buildup of material, or adulteration with lubricants, dirt or sanitizing agent. lUtensils, transfer piping and cosmetic contact surfaces of equipment are well-maintained and clean and are sanitized at appropriate intervals. lCleaned and sanitized
55、 portable equipment and utensils are stored and located, and cosmetic contact surfaces of equipment are covered, in a manner that protects them from splash, dust or other contamination. l在处理，生产，流转用途的设备和器具必须有适当的设计，原料和工艺。并通过以避免因灰尘等原因造成材料的腐蚀l器具，运转的管道和美容产品的生产设备必须间隔并整洁的放置l整洁的便携式设备和器具需被储存，生产美容用品的设备需被遮盖以避免
56、灰尘等污染物51Cosmetic / Drug GMPsPersonnellThe personnel supervising or performing the manufacture or control of cosmetics has the education, training and/or experience to perform the assigned functions. lPersons coming into direct contact with cosmetic materials, finished products in bulk or cosmetic co
57、ntact surfaces, to the extent necessary to prevent adulteration of cosmetic products, wear appropriate outer garments, gloves, hair restraints etc., and maintain adequate personal cleanliness. lConsumption of food or drink, or use of tobacco is restricted to appropriately designated areas. 52Cosmeti
58、c / Drug GMPsRaw MaterialslRaw materials and primary packaging materials are stored and handled in a manner which prevents their mix-up, contamination with microorganisms or other chemicals, or decomposition from exposure to excessive heat, cold, sunlight or moisture. lContainers of materials are cl
59、osed, and bagged or boxed materials are stored off the floor. lContainers of materials are labeled with respect to identity, lot identification and control status. 53Cosmetic / Drug GMPsRaw Materials (continued)lMaterials are sampled and tested or examined in conformance with procedures assuring the
60、 absence of contamination with filth, microorganisms or other extraneous substances to the extent necessary to prevent adulteration of finished products. Pay particular attention to materials of animal or vegetable origin and those used in the manufacture of cosmetics by cold processing methods with
61、 respect to contamination with filth or microorganisms. lMaterials not meeting acceptance specifications are properly identified and controlled to prevent their use in cosmetics.54Cosmetic / Drug GMPsProductionlThe equipment for processing, transfer and filling the utensils, and the containers for h
62、olding raw and bulk materials are clean, in good repair and in sanitary condition. lOnly approved materials are used. lSamples are taken, as appropriate, during and/or after processing, transfer or filling for testing for adequacy of mixing or other forms of processing, absence of hazardous microorg
63、anisms or chemical contaminants, and compliance with any other acceptance specification. lWeighing and measuring of raw materials is checked by a second person, and containers holding the materials are properly identified. 55Cosmetic / Drug GMPsProduction (continued)lMajor equipment, transfer lines,
64、 containers and tanks are used for processing, filling or holding cosmetics are identified to indicate contents, batch designation, control status and other pertinent information.lLabels are examined for identity before labeling operations to avoid mix-up. lThe equipment for processing, holding, tra
65、nsferring and filling of batch is labeled regarding identity, batch identification and control status. lPackages of finished products bear permanent code marks. lReturned cosmetics are examined for deterioration or contamination. 56Cosmetic / Drug GMPsLaboratorylRaw materials, in-process samples and
66、 finished products are tested or examined to verify their identity and determine their compliance with specifications for physical and chemical properties, microbial contamination, and hazardous or other unwanted chemical contaminants. lReserve samples of approved lots or batches of raw materials an
67、d finished products are retained for the specified time period, are stored under conditions that protect them from contamination or deterioration, and are retested for continued compliance with established acceptance specifications. 57Cosmetic / Drug GMPsLaboratory (continued)lThe water supply, part
68、icularly the water used as a cosmetic ingredient, is tested regularly for conformance with chemical-analytical and microbiological specifications. lFresh as well as retained samples of finished products are tested for adequacy of preservation against microbial contamination which may occur user reas
69、onably foreseeable condition of storage and consumer use. 58Cosmetic / Drug GMPsRecordslRaw materials and primary packaging materials, documenting disposition of rejected materials. lManufacturing of batches, documenting the: lKinds, lots and quantities of material used. lProcessing, handling, trans
70、ferring, holding and filling. lSampling, controlling, adjusting and reworking. lCode marks of batches and finished products. lFinished products, documenting sampling, individual laboratory controls, test results and control status. lDistribution, documenting initial interstate shipment, code marks a
71、nd consignees. 59Cosmetic / Drug GMPsLabelinglOn the principal display panel: lIn addition to the name of the product, the statements of identity and net contents, lOn the information panel: The name and address of the firm manufacturing the product or introducing it into interstate commerce. the li
72、st of ingredients (only on outer container) if intended for sale or customarily sold to consumers for consumption at home. lAny other warning statement necessary or appropriate to prevent a health hazard. Determine the health hazard or their basis for a warning statement. lAny direction for safe use
73、 of product. 60Cosmetic / Drug GMPsComplaintslThe kind and severity of each reported injury and the body part involved. lThe product associated with each injury, including the manufacturer and code number. lThe medical treatment involved, if any, including the name of the attending physician. lThe n
74、ame(s) and location(s) of any poison control center, government agency, physicians group etc., to whom formula information and/or toxicity data are provided. lWhether the firm voluntarily files Cosmetic Product Experience Reports (21 CFR 730). 61Cosmetic / Drug GMPsOtherlParticipating in the program
75、 of voluntary registration of: lCosmetic manufacturing establishments (21 CFR 710). lCosmetic product ingredient and cosmetic raw material composition statements (21 CFR 720). lCosmetic product experiences (21 CFR 730). lUsing a color additive which is not listed for use in cosmetics (21 CFR 73, 74,
76、 and 82) or which is not certified (21 CFR 80). lUsing a prohibited cosmetic ingredient (21 CFR 700). 62Cosmetic / Drug GMPsAn appropriate quality system to meet the applicable regulations63Appendix BMedical Device GMPs64Medical Device cGMPsGeneral controls include:Establishment Registration (use FD
77、A Form 2891) of companies which are required to register under 21 CFR Part 807.20, such as manufacturers, distributors, repackages and relabelers. Foreign establishments, however, are not required to register their establishments with FDA. Medical Device Listing (use FDA Form 2892) with FDA of devic
78、es to be marketed. Manufacturing devices in accordance with Good Manufacturing Practices (GMP) in 21 CFR Part 820. Labeling devices in accordance with labeling regulations in 21 CFR Part 801 or 809. Submission of a premarket notification 510(k) before marketing a device.65Medical Device cGMPsA medic
79、al device is:an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is:recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them, inte
80、nded for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or intended to affect the structure or any function of the body of man or other animals, and which does not achieve any of its primary intended purp
81、oses through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes.“66Medical Device cGMPsSubpart A General Provisions820.1 ScopeApplicable to manufacturers and importers of finished
82、 devices.Does not apply to manufacturers of components, but they are encouraged to use appropriate provisions as guidance.Establishes authorityAddresses foreign manufactures exporting devices to the U.S.Addresses exemptions or variances to the cGMPs.Subsection of definitions (820.3)67Medical Device
83、cGMPsSubpart B Quality System Requirements820.20 Management ResponsibilityQuality PolicyManagement with Executive responsibility establishes policy, objectives and commitment to quality.Management with Executive responsibility ensures quality policy is understood, implemented, and maintained through
84、out the organization.OrganizationEstablish and maintain adequate organizational structureResponsibility & AuthorityResourcesManagement Representative68Medical Device cGMPsSubpart B Quality System RequirementsManagement ReviewManagement with Executive responsibility reviews the suitability and effect
85、iveness of the quality system at defined intervals.Quality PlanningQuality PlanQuality PracticesResourcesActivitiesEstablished how the plan will be metQuality System ProceduresProceduresOutline of Structure820.20 Management Responsibility (continued)69Medical Device cGMPsSubpart B Quality System Req
86、uirementsQuality audit procedures shall be in place to assure:Quality system is in complianceDetermination of effectiveness of systemQuality audits Auditor shall be independentCorrective Actions takenAudit reportsAudits & reaudits results & dates are documented820.22 Quality Audit70Medical Device cG
87、MPsSubpart B Quality System Requirements820.25 PersonnelGeneralSufficient personnel with necessary education, training, background and experienceTrainingTraining proceduresPersonnel are adequately trainedDocumented71Medical Device cGMPsSubpart D Document Controls820.40 Document ControlsProcedure sha
88、ll be established and maintained to control all documents required by the cGMPsDocument approval and distributionDesignated individual(s)Available at useControlledDocument changesReviewed and approvedCommunicatedChange records description, identification of affected documents, signatures, approval d
89、ate, & effective date72Medical Device cGMPsSubpart E Purchasing Controls820.50 Purchasing ControlsProcedures for ensuring received product & services conform to specified requirements.Evaluations (suppliers, contractors, & consultants)Establish and maintain requirementsEvaluate & select on basis of
90、meeting requirements, document evaluationDefine control based on evaluation resultsEstablish & maintain records of acceptable suppliers73Medical Device cGMPsSubpart E Purchasing Controls820.50 Purchasing Controls (continued)Purchasing DataPurchasing data shall clearly reference specified requirement
91、s for purchased products.Include, where possible, agreement of suppliers to notify manufacturer (K-C) of changes in purchased product.Purchasing data shall be approved in accordance to Document Controls (820.40)74Medical Device cGMPsSubpart F Identification & Traceability820.60 IdentificationIdentif
92、icationEstablish and maintain procedures for identifying product during stages of receipt, production, and distribution to prevent mixups.75Medical Device cGMPsSubpart F Identification & Traceability820.65 TraceabilityTraceabilityEstablish and maintain procedures for identifying with a control numbe
93、r each unit, lot or batch of finished devices and where appropriate componentsProcedures shall facilitate corrective actionIdentification shall be documented in the Device History Record (DHR)76Medical Device cGMPsSubpart G Production & Process Controls820.70 Production & Process ControlsGeneralDeve
94、lop, conduct, control & monitor production process to ensure device conforms to its specifications. Process control procedures to ensure conformance.Documented instructionsMonitor & control process parameters, component/device characteristics during productionCompliance with standard/codesApproval o
95、f processes & process equipmentWorkmanship criteria documented standards or approved representative samples77Medical Device cGMPsSubpart G Production & Process ControlsProduction and Process ChangesEstablish and maintain procedures for changesValidatedDocumentedApprovedEnvironmental ControlWhere env
96、ironmental changes have an adverse effect of product, establish & maintain procedures to adequately control these conditionsEnvironmental control systems shall be periodically inspected for proper and adequate function. Document and review inspections 820.70 Production & Process Controls (continued)
97、78Medical Device cGMPsSubpart G Production & Process Controls820.70 Production & Process Controls (continued)PersonnelEstablish and maintain requirements health, cleanliness, personal practices & clothing of personnelTemporary personnel receive are appropriately trained or supervised by trained indi
98、vidualContamination ControlEstablish and maintain procedures to prevent contamination of equipment or productReasonable expectations79Medical Device cGMPsSubpart G Production & Process Controls820.70 Production & Process Controls (continued)BuildingsSuitable design and spacePrevent mixupsAssure orde
99、rly handlingEquipmentEnsure equipment used in manufacturing meets specified requirementsDocumented maintenance scheduleDocumented, periodic inspectionsAccessible adjustment limits80Medical Device cGMPsSubpart G Production & Process Controls820.70 Production & Process Controls (continued)Manufacturin
100、g MaterialWhere manufacturing could adversely effect product quality Procedures for use and removal of materialDocument removal or reduction of materialAutomated ProcessesWhere computers or automated data processing systems are used as part of production or the quality systemValidate computer softwa
101、reValidate changes prior to approval & issuanceDocumented validation activities & results81Medical Device cGMPsSubpart G Production & Process Controls820.72 Inspection, Measuring, & Test EquipmentControl of Inspection, Measuring, & Test EquipmentEnsures equipment is capable of producing valid result
102、s.Procedures for handling, preservation, storage and its accuracy and fitness for use are maintained.These activities shall be documented.CalibrationCalibration procedures shall be maintained.Remedial action for when accuracy & limits are not met.These activities shall be documented.82Medical Device
103、 cGMPsSubpart G Production & Process ControlsCalibration (continued) Calibration StandardsCalibrations standards must be traceable to national or international standardIf no standard exists, in-house standardCalibration RecordsEquipment identificationCalibration date, Due DateIndividualLocate record
104、 on, near equipment or readily available820.72 Inspection, Measuring, & Test Equipment (continued)83Medical Device cGMPsSubpart G Production & Process Controls820.75 Process ValidationWhere results cannot be verified subsequent inspection & test, process must be validated with approved proceduresAll
105、 validation activities shall be approved and documentedProcedures for monitoring & controlling of process parameters to ensure requirements continue to be met.Validation performed qualified individualThese activities shall be documentedChanges or deviations shall reviewed & evaluated, revalidation w
106、here appropriate, documented 84Medical Device cGMPsSubpart H Acceptance Activities820.75 Receiving, in-process, and Finished Device AcceptanceGeneralEstablish procedures for acceptance activities inspections, tests, or other verification activitiesReceiving Acceptance ActivitiesEstablish procedures
107、for acceptance of incoming product to specified requirement. Document acceptance or rejection.In-Process Acceptance ActivitiesEstablish procedures, where appropriate, to ensure specified in-process requirements are met. Ensure in-process product is controlled until test is completed or approved and
108、documented.85Medical Device cGMPsSubpart H Acceptance Activities820.75 Receiving, in-process, and Finished Device Acceptance (continued)Final Acceptance ActivitiesEstablish procedures for finished device acceptance to ensure run, lot, or batch meets acceptance criteria.Quarantine or adequately contr
109、ol devices until released.Complete activities required in Device Master RecordAssociated data & documentation is reviewedRelease is authorized by signature and dateAcceptance RecordsRecords shall part of the DHR and include:Acceptance activities performed with datesResults with signature(s)Equipment
110、 used where appropriate 86Medical Device cGMPsSubpart H Acceptance Activities820.86 Acceptance StatusIdentify by suitable means the conformance or nonconformance status of the product.This identification remains with product to ensure only product that has passed acceptance is distributed. 87Medical
111、 Device cGMPsSubpart I Nonconforming Product820.90 Nonconforming ProductControl of Nonconforming ProductEstablish procedures for controlling nonconforming product that addresses:IdentificationDocumentationEvaluationSegregationDispositionDetermine if evaluation or investigation is needed including no
112、tification of responsible organization.Document evaluation and any investigation.88Nonconformity Review & DispositionEstablish procedures for, responsibility, authority and process of the disposition of nonconforming product. This process is documented justification for use of nonconforming product
113、with signature(s).Establish procedures for rework of nonconforming product.RetestingReevaluationDocument rework & reevaluation (possible adverse effect of rework) in the DHR.820.90 Nonconforming Product (continued)Medical Device cGMPsSubpart I Nonconforming Product89Medical Device cGMPsSubpart J Cor
114、rective & Preventative Action820.100 Corrective & Preventative ActionEstablish procedures for CAPA that addresses:Analyzing method (statistical where necessary) ProcessesWork OperationsConcessionsQuality audit reportsQuality recordsService recordsComplaintsReturned productOther sourcesInvestigating
115、cause of nonconformity product, processes and quality system90Medical Device cGMPsSubpart J Corrective & Preventative Action820.100 Corrective & Preventative Action (cont.)Identify actions to correct and prevent nonconformities and other quality problems.Verify CAPA is effective and doesnt adversely
116、 affect product.Implementing change in process and procedures.Communicating information on quality issues for future prevention.Management reviewDocument all activities in this section91Medical Device cGMPsSubpart K Labeling & Packaging Control820.120 Device LabelingEstablish procedures to control l
117、abeling activities.Label IntegrityLabels printed and applied, remain legible throughout stages of distribution.Labeling InspectionLabeling released (storage or use) after inspection. Signature of individual(s) are documented in DHR.Labeling StorageProper storage manner that prevents mixups.Labeling
118、OperationsLabeling and packaging shall be controlled to prevent mixups.Label used on unit, lot or batch shall be documented in DHR.92Medical Device cGMPsSubpart K Labeling & Packaging Control820.120 Device Labeling (continued)Control NumberControl number shall accompany device through distribution.9
119、3Medical Device cGMPsSubpart K Labeling & Packaging Control820.130 Device PackagingDevice packaging shall be designed to protect product and prevent alteration or damage through customary distribution processing, storage, handling and shipping94Medical Device cGMPsSubpart L Handling, Storage, Distri
120、bution & Installation820.140 HandlingEstablish procedures to ensure mixups, damage, deterioration, contamination or other adverse effects to product do not occur.95Medical Device cGMPsSubpart L Handling, Storage, Distribution & Installation820.150 StorageEstablish procedures for storage areas that a
121、ddress prevention of the following:MixupsDamageDeteriorationContaminationOther adverse effectsProcedures shall ensure no obsolete, rejected, or deteriorated product is used or distributed.Stock rotation.Procedures for receipt from and dispatched to storage areas.96Medical Device cGMPsSubpart L Handl
122、ing, Storage, Distribution & Installation820.160 DistributionEstablish procedures for distribution of only released devices. Distribution records are maintained.Name & Address of consigneeIdentification and quantity shippedDate shippedControl numbers97Medical Device cGMPsSubpart L Handling, Storage,
123、 Distribution & Installation820.170 InstallationProvide device installation and use instructions.98Medical Device cGMPsSubpart M Records820.180 General RequirementsRecords required by part 820 shall have reasonable accessibility, readily available for the FDA, properly stored, and if automated shall
124、 be backed up.ConfidentialityRecords may be marked confidential to aid FDA in disclosing.Record Retention PeriodTime equivalent to design & expected life, not less than 2 years from the date of release.K-C Record Retention PolicyExceptionsManagement Review ReportsQuality AuditsSupplier Audit Reports
125、99Medical Device cGMPsSubpart M Records820.181 Device Master RecordMaintain a device master record (DMR) that includes or references location of:Device specifications drawings, composition, formulation, component specifications, & software specifications.Production process specifications equipment s
126、pecifications, production methods, production procedures, production environment specifications.Quality assurance procedures, specifications, and acceptance criteria100Medical Device cGMPsSubpart M Records820.181 Device Master Record (continued)Packaging and labeling specifications methods & process
127、esInstallation, maintenance, and servicing procedures and methods101Medical Device cGMPsSubpart M Records820.184 Device History RecordMaintain a device history record (DHR).Procedures shall ensure DHRs for each batch, lot, or unit are maintained.The DHR demonstrates device is made per DMR:The DHR sh
128、all include or reference location of:Manufacture datesQuantity manufacturedQuantity released for distributionAcceptance recordsPrimary label and labeling used for each production unitControl number used102Medical Device cGMPsSubpart M Records820.186 Quality System RecordMaintain a quality system rec
129、ord (QSR).The QSR shall include or reference location of procedures and documentation required by part 820.Quality Manual103Medical Device cGMPsSubpart M Records820.198 Complaint FilesMaintain complaint files. Establish procedures for receiving, reviewing, & evaluating complaints by a formally desig
130、nated unit. Procedures shall ensure that:All complaints are addressed uniformly & timelyOral complaints are documentedComplaint is evaluated to determine if FDA reporting is necessary - eventDetermine if complaint requires an investigation. Document reasons for not investigating.Review complaint on
131、possible failure of a device, labeling, or packaging not meeting specifications104Medical Device cGMPsSubpart M Records820.198 Complaint Files (continued)An event complaint shall be separated in the complaint files. In addition to the information required in this section, determine:Whether device fa
132、iled to meet specificationWhether device was being used for treatment or diagnosisRelationship of the device to the event105Medical Device cGMPsSubpart M Records820.198 Complaint Files (continued)When investigation is made the record is maintained and includes:Name of deviceDate complaint was receiv
133、edAny control numberName, address, & phone number of complainantComplaint nature and detailsInvestigation dates and resultsCorrective action takenReply to the complaint106Medical Device cGMPsSubpart M Records820.198 Complaint Files (continued)If complaint unit is located at a site separate from the
134、plant, complaints and investigation records shall be reasonably accessible to the plant.Complaint unit outside U.S., records are to be located:In U.S. with manufacturers recordsInitial distributor107Medical Device cGMPsSubpart O Statistical Techniques820.250 Statistical TechniquesEstablish procedures to identify valid statistical techniques used for verifying process capability and product characteristics.Procedures for developing and reviewing sampling plans. Changed plans are to be reviewed. These activities shall be documented.
