1、Objectives 培訓目的Introduction to GMPs?良好消費操作規范GMPs) 概述Why do we need GMPs我們為什么需求GMPs？When to we use GMPs?我們何時需求用到GMPs？General Overview of basic cGMP RequirementsCGMP根本要求總攬Key differences from the QMS與質量管理體系的關鍵區別Implementing for success勝利的方法1.Introduction to GMPs 良好消費操作規范引言GMPs defined History Applicat

2、ions GMPs 定義歷史適用范圍2.cGMPs Overview最新食品及藥物消費質量管理規范概要North Asia Quality Managers MeetingMarch 6, 2007Taipei Taiwan 北亞質量經理睬議 2007，3，6，臺北，臺灣3.Current Good Manufacturing Practices (cGMP) 最新食品及藥物消費質量管理規范Good Manufacturing Practices are.the current minimum guidelines for controlling the manufacturing, proc

3、essing, 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.消費管理規范是指。現行是指用以控制消費，進程，包裝和堅持藥品的最小方針，以此確保產品固有的數量及質量，并平安的被運用。4.GMP History GMP歷史Food and Drug Administration - Federal Food, D

4、rug and Cosmetic Act of 1938, as Amended: 1938年美國聯邦政府食品藥物管理規范規定：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.經過制止次級或被錯誤標志的食品，藥品，設備和化裝品國際貿易中的變動，以確保消費者的

5、利益不被危險性的或者帶有欺騙性的標簽和包裝的產品所損害。5.Food and Drug Administration 食品，藥品規程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 laws. 美國食品藥物管理局是經過實施美國

6、聯邦政府食品藥物控制及其他相關公眾安康法規，以確保美國消費者安康的公眾機構。6.Food and Drug Administration 食品和藥物控制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 as it should be)Manu

7、factured in compliance with applicable cGMPs美國聯邦政府食品藥物控制根本要求產品用途平安性藥品及設備有效運用未滲入次品如產品包含成分，僅有成分等無錯誤標志如標簽按照可行的最新食品及藥品消費質量規范進展消費7.Why do we need GMPs 我們為何需求藥品消費管理規范？Where is K-C going?LiabilityCompliance (FDA audits and reports)KC在哪些方面實施？職責承諾 (美國聯邦政府食品藥物管理局審核和報告8.K-C Direction K-C引言“A host of internal a

8、nd 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) 一系列內外部的挑戰正隨著金伯利發生著強大的變化。因此，我們正在朝著全球領先的安康衛消費品公司而努力著。摘自KC企業內部GBP網9.K-C Expectations KC的期望Corporate

9、 Integrity and ExpectationsProduct Safety ClearancesMeets Customer RequirementsOnly Approved MaterialsProperly and Effectively PackagedAccurately Branded and LabeledCorporate Manufacturing StandardsEnsure inspection readiness企業誠信和展望產品平安性滿足客戶要求僅被認可的資料合理有效的包裝準確的商標及標識企業消費規范平安監查預備10.Why cGMPs？為何實施cGMPs?

10、Its good businessProtect our consumersProtect our businessCustomer requirementsMaintain regulatory complianceRules for producing Safe and Clean ProductsPart of an appropriate Quality System良好的商機維護我們消費者的利益維護我們的商業時機客戶要求遵守規范的承諾產品平安性和整潔度的規范適當的質量體系11.GMPs are part of an “Appropriate Quality System GMPs是特

11、有的質量體系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 all GMP requirements金伯利質量管理體協要求指一切針對特有的質量體系而調整的要求ISO

12、13485指一切針對特有的質量體系而調整的要求ISO 9001不包含一切的GMP要求12.Legal Responsibilities 法律責任Must comply with the Federal Food, Device, Drug, and Cosmetic ActMust comply with the Fair Packaging and Labeling ActMust comply with Regulations issued under the authority of these Laws Enforced as part of the FD&C Act必需遵照美國聯邦政

13、府食品，設備藥物控制規程必需遵照美國公平包裝標式法必需遵照由上述權威法律所簽署的相關規章必需實施美國聯邦政府食品藥物控制規程13.When would we use GMPs? 何時運用GMPs？Production of regulated productsCustomer requirementsBusiness requirementsProtect the brand or businessProtect our C/S/C/U. 符合規那么的產品消費客戶要求商業要求維護品牌和商業維護我們的 C/S/C/U14.Also known as 21 CFR 820, Part 820, c

14、GMPApplies 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作為最新食物藥品消費質量規范章程，章節820適用一切醫療產品商絕大多數級別一的產品免除設計方面的控制一些風險較小的級別一的產品可免除除了處置贊揚和堅持記錄以外的其他要求FDA Quality Sy

15、stem Regulation 美國聯邦政府質量體系規章15.Medical Device cGMPs 醫療設備動態藥品消費管理規范Medical Device Classes:醫療設備等級Class I 等級Class 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 Class II or Class III devices. Class I device

16、s are subject to General Controls as are Class II and Class III devices.一級別的產品受調整的控制，并相對于級別二和三而言，在設計上較為簡單但對運用者幾乎沒有任何的損傷。一級別的產品在常規控制中和級別二三一樣。Examples of Class I devices:Unscented Pads or LinersExamination glovesAdult incontinence exempt一級別產品引例：無氣味的襯墊測試手套Note:Most Class I devices are exempt from the p

17、remarket notification and/or good manufacturing practices regulation.留意：大多數一級品除了先期市場告知外，都必需遵守良好的消費實際定律。16.Medical Device cGMPs 醫療產品的最新消費質量操作規范Class II 等級IIClass II devices are those for which general controls alone are insufficient to assure safety and effectiveness, and existing methods are availab

18、le to provide such assurances. In addition to complying with general controls, Class II devices are also subject to special controls. 二級別的產品是指那些在普通控制下還未足夠保證平安性能及效果的情況下，并存有其他技術以更好確實保其平安性，除普通控制之外，二級別的產品還受控于特殊控制。Examples of Class II devices:二級別產品舉例：Surgical drapes 外科醫用臺布Tampons 止血棉塞17.Medical Device cG

19、MPs 醫療產品的cGMPsClass III 等級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 special controls.級別三是最嚴厲的級別，三級別的產品是指除了普通和特殊控制外，還未有足夠的信息以確認產品的平安性的產品。Class I

20、II 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. 級別三的產品通常是那些用以支持和維護人類生活，并防止發生人體損傷或潛在及不合理的損傷風險的具有本質重要性的產品。Example of Class III device: 級別三的產品舉例

21、：implantable pacemaker 植入式心臟起博器 18.Medical Device Reporting (21CFR 803)Corrections, Removals and Withdrawals (21CFR 806)Labeling (21CFR 801) Electronic Records, Electronic Signatures (21CFR 11)Registration & Listing (21CFR 807)Quality System Regulation (21 CFR 820) with exemptions醫療產品報告更正，解除標注電子記錄，電

22、子簽名登記和名錄質量體協規章含免除部分What FDA Regulations Apply? 美國聯邦政府食品藥物管理規定適用什么？19.CE Marking - Medical Device Directive (MDD 93/42/EEC) if the product is distributed in the European UnionDevices must meet the essential requirements in Annex I.Technical documentation is required as outlined in Annex VIICE mark is

23、 affixed to the product in accordance with the procedure described in Annex XII.CE標志-醫療產品指點，假設該產品分售到歐洲聯盟產品必需符合必需的要求見附錄I技術文檔要求在附錄VII概述CE標志必需按照附錄XII中描畫的進程貼上What Other Quality System Standards Apply?其他質量體系規范適用什么？20.Cosmetic Products 美容用品“Articles, other than soap, intended to be rubbed, sprinkled, or s

24、prayed 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.那些除了肥皂外用于使身體清潔美觀等的任何噴霧或洗滌用品，并對身體不呵斥任何的損傷。21.cGMPs Cosmetic Products美容用品的消費質量操作規范cGMPs - O

25、NLY 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最新消費質量操作規范-僅是個方針消費者必需對產品的平安性擔任如不可有次品無任何有毒物質金伯利的消費質量操作規范適用于產品的制造，儲存，分銷.FDA Facility Regist

26、rationCosmetic Products 美國聯邦政府美容用品注冊None required by statuteVOLUNTARY registration allowed (21CFR 710)Registration of each manufacturing and packaging facilityIdentify company name, address and product name in registration法規未要求的自行的注冊每個消費及包裝設備的注冊公司稱號，地址和產品稱號的注冊.Definition of Adulterated Product 次品的定義

27、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 product含有任何有污染或有害的在產品運用情況下可引起損傷的物質有部分或完全污物在有污物情況下消費的集裝箱有能呵斥產品損害物質的.Definition of

28、 Misbranded Product 錯誤標志產品的定義False and misleading labelingFailure to label w/name and address of mfg., pkg., or distributorLacks net content statementNoncompliance of required labelingNonconforming colors錯誤的標志標志上未印有分量和分銷商缺乏凈含量未確認的顏色.Overview of GMPs GMPs總攬Medical Devices 醫療產品Cosmetics 美容產品26.cGMPs f

29、or Medical Devices醫療產品的最新消費操作規范A. General Provisions 普通規定B. Quality System Requirements 質量體系要求C. Design Controls 設計控制D. Document Controls 文檔控制E. Purchasing Controls 采購控制F. Identification and Traceability 驗明和可追述性G. Production and Process Controls 產品及進程控制H. Acceptance Activities 可接受性I. Nonconforming P

30、roduct 非確認產品J. Corrective and Preventive Action 糾正及預防措施K. Labeling and Packaging Control 標簽和包裝控制L. Handling, Storage, Distribution, and Installation 處置，貯藏，分銷和安裝M. Records 記錄N. Servicing 效力O. Statistical Techniques 技術27.GMP Linkage to the QMS 消費操作規范和質量管理體系的聯絡What are the similar requirements?What are

31、 the key differences?What is the impact of the required changes?要求的類似處？關鍵差別？要求變化的作用？28.QMS/GMP Similarities 質量管理體系和消費操作規范的類似處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.質量管理體系是作

32、用于符合外部和全球性的規范質量管理體系高級別的要求必需符合可調整的要求之內29.Specific requirements for GMPs GMPs的特殊要求Complaints ProcessDesign Verification & ValidationDevice Master Record (DMR)Device History Record (DHR)Quality System RegulationElectronic RecordsProcess ValidationChange ControlsRegistrations and ApprovalsOthers贊揚方法設計認可

33、和確認產品主要記錄產品歷史記錄質量體系規章電子記錄方法確認改動控制登記和認可其他30.Any written, electronic or oral communication that alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness or performance of a device after it is released for distribution.任何落筆的，電子的或口頭交流的關于在產品出產或分銷后，對產品的闡明，質量，耐久

34、性，可靠和平安性的不完備的申訴。What is a Complaint?什么是贊揚31.Requirements are discussed in 21CFR 820.198 要求在21CFR 820.198被討論過The regulation requires 規章要求Documented procedures 進程文檔記錄Timely and uniform processing 及時一致的處置Process for evaluation/investigation 評價方法Adverse event consideration (serious injury or death)不利方面的

35、思索嚴重的損傷或死亡Additional requirements apply to complaints alleging serious injury or death (21 CFR 803)正對嚴重損傷或死亡的申訴的額外要求21CFR803)What About Complaint Files? 贊揚文件32.A compilation of records containing the production history of a finished device. 記錄需包含每個廢品的消費歷史A DHR includes DHR包含 Dates of manufacture 消費日

36、期Quantity manufactured and released 數量和消費Acceptance records 可接受記錄Primary identification label 主要確認標志Device identification and lot number 產品確認和消費標號What is a DHR?DHR是什么？33.Maintained at the manufacturing site or otherwise reasonable accessible.維護消費地或合理進入Legible and complete (errors must be appropriate

37、ly corrected) 易讀的和完成的錯誤必需適當糾正Retained for the life of the product (minimum 2 years from date of release).產品壽命需維持從消費日期起至少2年Exceptions include Management Review, Quality Audits and Supplier Audits.特殊情況包含管理檢閱，質量審核和供應商審核Record Requirements 記錄要求34.Additional requirementsElectronically stored must be back

38、ed upElectronically created must comply with Part 11 requirementsElectronically signed must comply with Part 11 requirementsCSV Roadmap kcc/mis/ProgramOffice/ICS/CSV/CSVRoadMap/CSVFlow/CSV%20Roadmap_frame.htm額外要求電子貯藏-必需后備電子生成-必需與11章節要求一致電子簽署-必需與11章節要求一致CSV途徑httpkcc/mis/ProgramOffice/ICS/CSV/CSVRoadM

39、ap/CSVFlow/CSV%20Roadmap_frame.htmElectronic Record Requirements 電子記錄要求35.Design Verification and Validation, Process Validation 設計及方法確認和同意Design Verification and ValidationsMust verify design “Output meets “Input.Must validate design under normal operating conditions with production product. Design

40、 validation must Risk assessments.設計確實認和同意必需確認設計從消費和出產的一致必需在常規產品消費操作的情況下同意設計設計同意必需經過風險評價Process Validations 方法同意Where results of a process can not be verified, a process shall be validated, i.e., bioburden, cleaning, sanitization, etc. 當一種方法的結果不被查證時，36.Change Requirements 改動要求Change control process

41、for the identification, documentation, validation, or where appropriate verification, review and approval of changes before implementation. 改動控制進程是在改動實施之前，針對改動的，審閱，查證，認可隨后做出相應的審批，法律批文和文檔的過程。These changes include, but are not limited to: 這些改動包含以下方面但不僅限于此：Design 設計Process 進程Software 軟件Cleaning 清潔Sanit

42、ization 去除干凈37.GMP Controls - What needs to be in place? 什么適當的方面需求GMP控制Understand the scope, risk and regulationsAssess risks HACCPProduct History領會范圍，風險及規章評價風險-HACCP 危害分析關鍵控制點產品歷史38.Risk Assessment Scope 風險評價范圍39.How do we assess GMP risks?我們如何評價GMP風險？HACCP is a proactive systematic approach to the

43、 identification, assessment of risk and severity, and control of biological, chemical, and physical hazards/contamination associated with a product, production process or practice. HACCP是一種較有體系的方法，使產品在消費實際過程中，對產品生物化學物理技藝等方面的風險及嚴肅性的審查及評價。 40. Why use HACCP?為何適用危害分析關鍵控制點Its all about making Safe and C

44、lean products and meeting Good Manufacturing Practices! 一切都是為了消費平安整潔的產品Regulatory requirements 調整要求Competitive advantage for identification of design issues early 設計版本及早確實認具有競爭性的優勢Protection for product liability awards 產品審查責任的維護Learn about HACCP as a tool for assessing contamination risks 學習HACCP作為

45、評價混淆風險的工具41.HACCP for Diapers - Example42.GMP Next Steps GMP下階段Impact on North AsiaKoreaChinaTaiwan對北亞的影響韓國中國臺灣Plans for implementation 方案實施Training 培訓Project Management 工程管理43.The 3 Keys to Success with GMPs GMPs勝利的三點關鍵Critical Start Infrastructure and SystemsAvoid Surprises Communicate and plan Ea

46、rlyProduct Design, Development, Process and Approvals開場評論-構造和體系防止不測事件-及早溝通與方案產品-設計，開展進程和認可44.Resources 資源GRSARegulatory AffairsCART (Compliance and Resource Team)Global Capability TeamsBusiness Quality Leaders規程CART資源團隊全球力量團隊商業質量指點45.Questions 問題46.Appendix A 附錄ACosmetic and Drug GMPs美容及藥品消費質量操作規范47

47、.Cosmetic / Drug GMPs 美容及醫藥消費質量操作管理規范Buildings and Facilities 消費場地及設備Buildings 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 mainte

48、nance. Floors, walls and ceilings are constructed of smooth, easily cleanable surfaces and are kept clean and in good repair. Fixtures, 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

49、 finished products in bulk. 消費場地是指用于適宜尺寸，設計的美容產品的消費和儲存，并用于設備的堆放，日常原料的儲存，衛生的操作以及適度的清潔和維護。地板，墻壁和天花板必需平整的建筑，并較易的可做外表清潔和良好的維修。安裝物，電線以及管道等必需被合理安裝，以防止有房屋滲漏景象導致機械外表，籮筐里面的廢品的破損。48.Cosmetic / Drug GMPs美容及醫藥消費質量操作管理規范Buildings and Facilities (continued)Lighting and ventilation are sufficient for the intended

50、operation and comfort of personnel. Water supply, washing and toilet 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. 照明以及通風必需足以使個人溫馨和順應操作水供應，

51、洗手間設備，地面排水渠道和排污系統必需足以滿足衛生操作和設備清潔也必需滿足雇員個人的清潔49.Cosmetic / Drug GMPs美容及醫藥消費質量操作管理規范Equipment 設備Equipment and utensils used in processing, holding, transferring and filling are of appropriate design, material and workmanship to prevent corrosion, buildup of material, or adulteration with lubricants, d

52、irt or sanitizing agent. Utensils, transfer piping and cosmetic contact surfaces of equipment are well-maintained and clean and are sanitized at appropriate intervals. Cleaned and sanitized portable equipment and utensils are stored and located, and cosmetic contact surfaces of equipment are covered

53、, in a manner that protects them from splash, dust or other contamination. 在處置，消費，流轉用途的設備和器具必需有適當的設計，原料和工藝。并經過以防止因灰塵等緣由呵斥資料的腐蝕器具，運轉的管道和美容產品的消費設備必需間隔并整潔的放置整潔的便攜式設備和器具需被儲存，消費美容用品的設備需被遮蓋以防止灰塵等污染物50.Cosmetic / Drug GMPsPersonnelThe personnel supervising or performing the manufacture or control of cosmet

54、ics has the education, training and/or experience to perform the assigned functions. Persons coming into direct contact with cosmetic materials, finished products in bulk or cosmetic contact surfaces, to the extent necessary to prevent adulteration of cosmetic products, wear appropriate outer garmen

55、ts, gloves, hair restraints etc., and maintain adequate personal cleanliness. Consumption of food or drink, or use of tobacco is restricted to appropriately designated areas. 51.Cosmetic / Drug GMPsRaw MaterialsRaw materials and primary packaging materials are stored and handled in a manner which pr

56、events their mix-up, contamination with microorganisms or other chemicals, or decomposition from exposure to excessive heat, cold, sunlight or moisture. Containers of materials are closed, and bagged or boxed materials are stored off the floor. Containers of materials are labeled with respect to ide

57、ntity, lot identification and control status. 52.Cosmetic / Drug GMPsRaw Materials (continued)Materials are sampled and tested or examined in conformance with procedures assuring the absence of contamination with filth, microorganisms or other extraneous substances to the extent necessary to prevent

58、 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 respect to contamination with filth or microorganisms. Materials not meeting acceptance specifications are properly i

59、dentified and controlled to prevent their use in cosmetics.53.Cosmetic / Drug GMPsProductionThe equipment for processing, transfer and filling the utensils, and the containers for holding raw and bulk materials are clean, in good repair and in sanitary condition. Only approved materials are used. Sa

60、mples 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 microorganisms or chemical contaminants, and compliance with any other acceptance specification. Weighing and measuring of raw ma