药品生产验证总计划VMP.docx

1、药品生产验证总计划VMPPharmacy Manufacturing Unit Validation Master Plan (VPM).General NotesAims of Qualification and ValidationAny significant changes to, premises, equipment or processes, which may affect the quality of the final product, directly or indirectly, should be qualified and validated. The key el

2、ements of a qualification and validation program should be clearly defined and documented in a Validation Master Plan. The process should establish and provide documentary evidence that: premises, supporting utilities, equipment and processes have been designed in accordance with the requirements of

3、 GMP. This normally constitutes the Design Qualification or DQ and includes confirmation that the premises, supporting utilities and equipment have been built and installed in compliance with their design specifications (this constitutes Installation Qualification or IQ) and that they operate in acc

4、ordance with their design specifications (this constitutes Operational Qualification or OQ).A specific process will consistently produce a product meeting its predetermined specifications and quality attributes (this constitutes Process Validation or PV. The term Performance Qualification or PQ may

5、be used also).PurposeThe VMP is intended to be a live document that supports the design and construction of any production facility, its subsequent operation, maintenance and changes to the facility for its life span. The VMP should present an overview of the entire validation operation, its organis

6、ational structure, its content and planning. The core of the VMP is the list/inventory of items to be validated and the planning schedule.The VMP should provide your organisation with the basis for validation and quality system activities required for cGMP compliance. This will enable any sterile or

7、 non-sterile medicinal product that is produced, processed, stored or distributed, by the manufacturing unit, to be validated under the control of an appropriate quality system.The VMP should provide a cross-reference to other documents, such as SOPs, validation protocols, validation reports, and de

8、sign plans. A rationale for the inclusion or exclusion of validations, from the approach adopted should be included.VMP DocumentThe VMP template is attached for completion as appropriate the document should be cross-referenced with design specifications, design plans and other relevant documentation

9、. Appendices should contain all the relevant documentation referenced or stated in the VMP.Company LogoCompany NameVALIDATION MASTER PLANDocument Reference:Reference NumberRevision:Draft Number or Revision NumberDate of Issue:_/_/_Page:2 of _Approved by:Name:Signature:Date:Production Team LeaderQual

10、ity Control OfficerSenior EngineerCompiled byTitle:Name:Signature:Date:Validation EngineerCONTENTS1.0 LIST OF ABBREVIATIONS 52.0 Document Revision History 63.0 Validation Steering Committee 73.1 Membership of Validation Steering Committee 73.2 Responsibilities 83.2.1 Pharmacy Production Team Leader

11、83.2.2 Pharmacy Senior Production Technician 83.2.3 Trust Senior Engineer 83.2.4 Pharmacy Quality Control Officer 83.2.5 Validation Engineer 84.0 Introduction 94.1 Purposes of VMP 94.2 Overview of Project 94.3 Validation Philosophy 95.0 Regulatory Standards And Guidelines 106.0 Description of Produc

12、ts and Processes 116.1 Introduction 116.2 Product Groups 116.3 Processes 116.4 Product Storage and Distribution 117.0 PROJECT DESCRIPTION 127.1 Site Location 127.2 Facility Design and Layout. 127.3 Production Suites 127.3.1 Zone 1, Non-Sterile Manufacturing 127.3.2 Zone 2, Preparation of Cytotoxic P

13、roducts and Parental Nutrition Products 128.0 Equipment and services to be Validated 148.1 Impact Assessment 148.2 Risk Assessment 148.3 Validation Matrix 149.0 Validation Activities 159.1 Validation Activities 159.1.1 User Requirement Specification (URS) 159.1.2 Technical Specification 159.1.3 Impa

14、ct Assessment 159.1.4 Design Review/Qualification 159.1.5 Factory Acceptance Tests 159.1.6 Commissioning 169.1.7 Installation Qualification 169.1.8 Calibration 169.1.9 Operational Qualification 179.1.10 Standard Operating Procedures 179.1.11 Performance Qualification 189.1.12 Combined Qualifications

15、 (I/OQ & O/PQ) 189.1.13 Process Validation (PV) 189.1.14 Cleaning Validation 189.1.15 Analytical Method and Laboratory Equipment Validation 199.1.16 Product Storage and Distribution Validation 199.1.17 Relocated Equipment 199.1.18 Computer Validation Testing 209.1.19 Computer Operational Qualificati

16、on 错误！未定义书签。9.2 Validation Reports 209.3 Validation History File 2010.0 CHANGE CONTROL 2110.1 VMP Revisions 2110.2 Change Control Initiation 2110.3 Definition of Change 2110.4 Change Control Procedure 2111.0 QUALITY MANAGEMENT 2212.0 SCHEDULE OF STANDARD OPERATING PROCEDURES 2313.0 PREVENTATIVE MAIN

17、TENANCE 2414.0 SCHEDULE OF WORK PACKAGES 2515.0 TRAINING 2616.0 Responsibilities and APPROVAL OF Protocols and DOCUMENTATION 2716.1 Protocol Responsibility 2716.2 Approval of Protocols and Reports 2716.3 Approval Of Validation Documentation 27AppendicesAnnex 1 Cleaning validation master planAnnex 2

18、Analytical method validation master plan1.0 LIST OF ABBREVIATIONSAHUAir Handling UnitNHSNational Health ServiceBPBritish PharmacopoeiaO & MOperation and MaintenanceBSBritish StandardOQOperational QualificationCFRCode of Federal RegulationsP&IDPiping and Instrumentation DiagramcGMPCurrent Good Manufa

19、cturing PracticePCAPatient Controlled AnalgesiaCIPClean In PlacePFDProcess Flow DiagramCIVACentralised Intravenous AdditivesPIDProportional Integral and Derivative Comm.CommissioningplcProgrammable logic controllerCPUCentral Processing UnitPQPerformance QualificationDCDirect CurrentPVProcess Validat

20、ionDCCDesign Change ControlQAQuality AssuranceDQDesign QualificationQCQuality ControlDRDesign ReviewQMSQuality Management SystemEDREnhanced Design ReviewRARisk AssessmentEPEuropean PharmacopoeiaRev.RevisionEUEuropean UnionSATSite Acceptance TestFATFactory Acceptance TestSIP Sterilise/Sanitise In Pla

21、ceFDAFood and Drug AdministrationSOPStandard Operating ProcedureFDSFunctional; Design StatementSVASmall Volume AmpoulesGAGeneral ArrangementTPNTotal Parenteral NutritionGAMPGood Automated Manufacturing PracticeURSUser Requirement StatementGCPGood Cleaning PracticeVCCValidation Change ControlGEPGood

22、Engineering PracticeVMPValidation Master PlanGLPGood Laboratory PracticeVSCValidation Steering CommitteeHACCPHazard And Critical Control PointVTFValidation Technical FileHS&EHealth Safety And EnvironmentWFIWater For InjectionHTMHealth Technical MemorandumHVACHeating, Ventilation and Air Conditioning

23、IAImpact AssessmentIQInstallation QualificationISOInternational Standards OrganisationISPEInternational Society of Pharmaceutical EngineersLVFLarge Volume FluidsMCAMedicines Control Agency2.0 Document Revision HistoryRevisionDetailsDateAuthorDraft 1 Initial draft _/_/_Draft 2_/_/_Draft 3_/_/_Revisio

24、n 00Original issue. _/_/_Revision 01_/_/_3.0 Validation Steering Committee3.1 Membership of Validation Steering CommitteeThis Validation Master Plan has been compiled by a Validation Steering Committee (VSC) who will also manage its execution. The members of the VSC are listed below and by their sig

25、natures acknowledge their responsibilities to ensure that all validation activities are carried out as described in this Validation Master Plan (VMP) and its annexes.It is recommended that the members of the VSC should include, but is not limited to the following areas of responsibility and expertis

26、e: Pharmacy Production Team Leader Pharmacy Senior Production Technician Trust Senior Engineer Pharmacy Quality Control Officer cGMP Consultant Validation SpecialistAdditional members co-opted onto the VSC shall also sign below before undertaking any activities associated with this VMP.Name (Print)P

27、osition/CompanyInitialSignatureDate3.2 ResponsibilitiesWith respect to the activities outlined in this VMP and its Annexes, including cleaning, manufacturing practices and analytical methods, the responsibilities of key VSC members are outlined below. Their responsibilities with respect to the overa

28、ll operation are included where this may have an impact upon validation activities. Approval of new or amended documentation should be accomplished with the minimum of delay, ideally within 2 working days, to facilitate the efficient operation of the facility3.2.1 Pharmacy Production Team LeaderThe

29、pharmacy production team leader is responsible for: Ensuring that appropriately qualified personnel are appointed. Ensuring production processes are in accordance with cGMP requirements. Facilitating validation activities. Training and management of personnel. Approval of user functional aspects of

30、validation protocols Approval of working production documents for overall content.3.2.2 Pharmacy Senior Production TechnicianThe pharmacy operations representative is responsible for Completion of batch records. Operating procedures. Training of personnel.3.2.3 Trust Senior Engineer Ensuring that systems/equipment are appropriate for their purpose. Maintenance of systems/equipment. Maintenance procedures. Calibration policy and proc