药品生产验证总计划VMP.docx

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1、PHARMACY 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 elements of a

2、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 GMP. This n

3、ormally 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 accordance with

4、 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 be used also

5、).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 organisational stru

6、cture, 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 non-sterile

7、 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 design plans.

8、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. Appendices

9、 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 LeaderQuality Control

10、OfficerSenior EngineerCompiled byTitle:Name:Signature:Date:Validation EngineerNEW ZEALAND HEALTHCARE PHARMACISTS ASSOCIATIONCompounding Nutrition & Oncology SIGDoc. Ref.:NZHPA CNO-SIGPage:31 of _Author:VALIDATION MASTER PLANDate:Revision 01CONTENTS1.0LIST OF ABBREVIATIONS52.0DOCUMENT REVISION HISTOR

11、Y63.0VALIDATION STEERING COMMITTEE73.1Membership of Validation Steering Committee73.2Responsibilities83.2.1Pharmacy Production Team Leader83.2.2Pharmacy Senior Production Technician83.2.3Trust Senior Engineer83.2.4Pharmacy Quality Control Officer83.2.5Validation Engineer84.0INTRODUCTION94.1Purposes

12、of VMP94.2Overview of Project94.3Validation Philosophy95.0REGULATORY STANDARDS AND GUIDELINES106.0DESCRIPTION OF PRODUCTS AND PROCESSES116.1Introduction116.2Product Groups116.3Processes116.4Product Storage and Distribution117.0PROJECT DESCRIPTION127.1Site Location127.2Facility Design and Layout.127.

13、3Production Suites127.3.1Zone 1, Non-Sterile Manufacturing127.3.2Zone 2, Preparation of Cytotoxic Products and Parental Nutrition Products128.0EQUIPMENT AND SERVICES TO BE VALIDATED148.1Impact Assessment148.2Risk Assessment148.3Validation Matrix149.0VALIDATION ACTIVITIES159.1Validation Activities159

14、1.1User Requirement Specification (URS)159.1.2Technical Specification159.1.3Impact Assessment159.1.4Design Review/Qualification159.1.5Factory Acceptance Tests159.1.6Commissioning169.1.7Installation Qualification169.1.8Calibration169.1.9Operational Qualification179.1.10Standard Operating Procedures1

15、79.1.11Performance Qualification189.1.12Combined Qualifications (I/OQ & O/PQ)189.1.13Process Validation (PV)189.1.14Cleaning Validation189.1.15Analytical Method and Laboratory Equipment Validation199.1.16Product Storage and Distribution Validation199.1.17Relocated Equipment199.1.18Computer Validatio

16、n Testing209.1.19Computer Operational Qualification错误！未定义书签。9.2Validation Reports209.3Validation History File2010.0CHANGE CONTROL2110.1VMP Revisions2110.2Change Control Initiation2110.3Definition of Change2110.4Change Control Procedure2111.0QUALITY MANAGEMENT2212.0SCHEDULE OF STANDARD OPERATING PROC

17、EDURES2313.0PREVENTATIVE MAINTENANCE2414.0SCHEDULE OF WORK PACKAGES2515.0TRAINING2616.0RESPONSIBILITIES AND APPROVAL OF PROTOCOLS AND DOCUMENTATION2716.1Protocol Responsibility2716.2Approval of Protocols and Reports2716.3Approval Of Validation Documentation27APPENDICESANNEX 1CLEANING VALIDATION MAST

18、ER PLANANNEX 2ANALYTICAL METHOD VALIDATION MASTER PLAN1.0 LIST OF ABBREVIATIONSAHUAir Handling UnitNHSNational Health ServiceBPBritish PharmacopoeiaO & MOperation and MaintenanceBSBritish StandardOQOperational QualificationCFRCode of Federal RegulationsP&IDPiping and Instrumentation DiagramcGMPCurre

19、nt Good Manufacturing PracticePCAPatient Controlled AnalgesiaCIPClean In PlacePFDProcess Flow DiagramCIVACentralised Intravenous AdditivesPIDProportional Integral and Derivative Comm.CommissioningplcProgrammable logic controllerCPUCentral Processing UnitPQPerformance QualificationDCDirect CurrentPVP

20、rocess ValidationDCCDesign Change ControlQAQuality AssuranceDQDesign QualificationQCQuality ControlDRDesign ReviewQMSQuality Management SystemEDREnhanced Design ReviewRARisk AssessmentEPEuropean PharmacopoeiaRev.RevisionEUEuropean UnionSATSite Acceptance TestFATFactory Acceptance TestSIP Sterilise/S

21、anitise In PlaceFDAFood and Drug AdministrationSOPStandard Operating ProcedureFDSFunctional; Design StatementSVASmall Volume AmpoulesGAGeneral ArrangementTPNTotal Parenteral NutritionGAMPGood Automated Manufacturing PracticeURSUser Requirement StatementGCPGood Cleaning PracticeVCCValidation Change C

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

23、r ConditioningIAImpact AssessmentIQInstallation QualificationISOInternational Standards OrganisationISPEInternational Society of Pharmaceutical EngineersLVFLarge Volume FluidsMCAMedicines Control Agency2.0 DOCUMENT REVISION HISTORYRevisionDetailsDateAuthorDraft 1 Initial draft _/_/_Draft 2_/_/_Draft

24、 3_/_/_Revision 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 an

25、d by their signatures 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 responsibilit

26、y and expertise: 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

27、Name (Print)Position/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 respec

28、t to the overall 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 T

29、eam LeaderThe 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 function

30、al aspects of 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 En

31、suring that systems/equipment are appropriate for their purpose. Maintenance of systems/equipment. Maintenance procedures. Calibration policy and procedures. Revision of O & M manuals for equipment/systems. Approval of validation protocols for content relating to engineering content.3.2.4 Pharmacy Q

32、uality Control Officer Ensuring appropriate Quality Control (QC) procedures are in place Provision and maintenance of auditable document storage systems. Approval of validation protocols for quality aspects. Approval of all working QC and production documents 3.2.5 Validation Engineer Identify and p

33、lan appropriate validation activities. Provide validation technical support and training. Ensure appropriate validation procedures are in place.4.0 INTRODUCTION4.1 Purposes of the VMPThe purposes of the VMP are to: Identify the members of the Validation Steering Committee. Identify Regulatory requir

34、ements. Identify and describe the facility, systems and equipment to be validated. Identify and describe products and processes to be validated. Identify the validation activities that will be undertaken. Identify the methods by which these activities will be undertaken. Identify the documentation r

35、equirements to support the above activities.4.2 Overview of ProjectThis VMP relates to a new facility, to be known as the _. In line with current GMP standards the new pharmacy will provide aseptically dispensed intravenous products and manufactured sterile and non-sterile products to _ Hospital pat

36、ients.4.3 Validation Philosophy The VMP is intended to be a live document that initially supports the design and construction of the facility and subsequently the operation, maintenance and change of the facility for its entire life. It will provide the basis for validation and quality system activi

37、ties required for cGMP compliance. This will enable the validated production, processing, storage and distribution of a range of sterile and non-sterile medicinal products under the control of an appropriate quality system. The VMP may be revised as appropriate to incorporate changes and/or addition

38、s to the facility and/or products.Using current pharmaceutical industry guidelines, the validation steps and activities will be designed to address all critical product attributes and process steps whilst minimising un-necessary work. This will be achieved by employing techniques such as Impact Asse

39、ssment and risk assessment, in order to focus validation activity onto those systems critical to product quality.The validation process will follow these basic group headings: Quality Plan Design Reviews FAT/Commissioning Installation Qualification SAT/Operational/Performance Qualification Process V

40、alidation Cleaning Validation Analytical Method ValidationThe validation activities will be incorporated into project design, construction programs and production schedules. The objective of this is to integrate similar activities, e.g. SAT with OQ, and thus reduce duplication of tests and checks to

41、 a minimum. Appendix D illustrates the relationship between project and validation stages.5.0 REGULATORY STANDARDS AND GUIDELINESThe following is a list of standards and guidelines deemed to be appropriate for this project. This list is not exhaustive and further regulations and guidelines will be u

42、sed where appropriate. The list will be reviewed and revised as necessary whenever a new revision of the VMP is issued.1. New Zealand Code of Good Manufacturing Practice for Manufacture and Distribution of Therapeutic Good, Part 1 Manufacture of Pharmaceutical Products, 1993.2. New Zealand Code of G

43、ood Manufacturing Practice for Manufacture and Distribution of Therapeutic Good, Part 3 Compounding and Dispensing, 1993.3. New Zealand Code of Good Manufacturing Practice for Manufacture and Distribution of Therapeutic Good, Part 3, Annex 1 Compounding of Sterile Pharmaceutical Products, 1995.4. PI

44、C/S Guide to Good Manufacturing Practice for Medicinal Products, 15th Jan 025. MCA Rules and Guidance for Pharmaceutical Manufacturers and Distributors, 2002.6. AS/NZS ISO14644.1:2002 : Cleanrooms and associated controlled environments Part 1: Classification and air cleanliness7. AS/NZS 14644.2:2002

45、 : Cleanrooms and associated controlled environments Part 2: Specifications for testing and monitoring to prove continued compliance with ISO 14644.18. AS/NZS ISO 14644.4:2002 : Cleanrooms and associated controlled environments Part 4: Cleanrooms and associated controlled environments - Design, construction and start-up9. ISO EN 14644.5:2004, Cleanrooms and Associated Controlled Environments Part 5: Cleanroom Operations.10. ISO 14644-7:2004 : Cleanrooms and associated controlled environments - Part 7: Separative devices (clean air hoods, gloveboxes, isolators and mini-environments)11. AS/NZS