Good Manufacturing Practice for Human Vaccines Derived from Bioengineered PlantsSlide 2Stages Involved in Regulating Biological ProductsSlide 4Slide 5Slide 6Slide 7Slide 8What is CGMP?Four Basic Elements of CGMP: “4Ms”Slide 11Organizational StructurePersonnel QualificationPersonnel ResponsibilitiesSlide 15DesignLightingSchedule of minimum air requirements for various manufacturing spacesSlide 19Slide 20Design, Size & LocationCleaning & MaintenanceAutomatic, Mechanical & Electronic EquipmentSlide 24ReceiptSamplingTestingRelease for UseSlide 29Written ProceduresValidationSlide 32Slide 33MaterialsPackaging and Labeling OperationsSlide 36Warehousing and DistributionSlide 38General RequirementsReserve SamplesSlide 41Master Production and Control Records(MPR)Batch Production and Control Records(BPR)Product Record Review (GMP Audit)Laboratory RecordsDistribution Records:Complaint FilesSlide 48Slide 49Slide 50Slide 51Slide 52Slide 53Slide 54Slide 55Slide 56Slide 57Slide 58Slide 59Slide 60Good Manufacturing Practice for Good Manufacturing Practice for Human Vaccines Derived from Human Vaccines Derived from Bioengineered PlantsBioengineered PlantsChung Keel Lee, Ph.D..JAN, 24~25, 20052I. Approval Process for Biological Products3Stages Involved in Regulating Biological ProductsPhase 1Phase 2 Phase 3******Preclinical R&DNotice of claimed investigational exemption for a new drug(IND application)Clinical research and development : Phase 1,2,3Developmental stageLicensing stagePost-licensing stageSafety reviewby NRA******4II. Related Regulations / Guidances5A.A.WHOWHO1. Guidelines on Good Agricultural and Collection Practices (GACP) for Medicinal Plants, 20032. Good Manufacturing Practices (GMP) for Pharmaceutical Products: main principles, TRS 908, 20033. Good Manufacturing Practices:supplementary guidelines for the manufacture of herbal medicinal products, TRS 863, 19964. Quality Control Methods for Medicinal Plant Materials, 19986B.B.EMEAEMEA1. Points to Consider on Good Agricultural and Collection Practice for Starting Materials of Herbal Origin, 20022. Points to Consider on Quality Aspects of Medicinal Products Containing Active Substances Produced by Stable Transgene Expression in Higher Plants, 20023. Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients, Q7A, ICH, 20007C.C.US FDAUS FDA1. Drugs, Biologics, and Medical Devices Derived from Bioengineered Plants for Use in Humans and Animals, 20022. Current Good Manufacturing Practice in Manufacturing, Processing Packing or Holding of Drugs: general, 21 CFR 210, 20043. Current Good Manufacturing Practice for Finished Pharmaceuticals, 21 CFR 211, 20044. Biologics, 21 CFR 600, 601 & 610, 20048III.III. Current Good Manufacturing Practice (CGMP) for Pharmaceutical Products9What is CGMP? Current Good Manufacturing PracticeThe minimal necessary level of operation and administration of facilities, methods and controls To manufacture drug products of consistently high quality (to assure that the product meets the requirements of the act as to safety and effectiveness which the product purports)21CFR210,21110Four Basic Elements of CGMP: “4Ms” “4Ms”“4Ms”Men MachineryMaterialsMethodsQualificationAdequate trainingProductsReagentsComponentsContainers & ClosuresLabelsManufacturingControl ValidationDocumentationBuildingsFacilitiesEquipmentTools11 Organization & Personnel12Organizational Structure ManagerManagerProductionProductionQuality ControlQuality ControlIndependence!Quality AssuranceQuality Assurance13Personnel Qualification  Background of education In-house training Extramural training…Needs training evaluation column14Personnel Responsibilities  Clean clothing  Protective apparel : Head, Face, Hand, Foot & Arm coverings  Illness or open lesions Good sanitation and health habits Authorized personnel only for limited-access areas15 Building & Facilities16Design The Size & ConstructionThe Size & ConstructionThe Flow of MaterialsThe Flow of MaterialsSpecifically Defined area Specifically Defined area To Facilitate cleaning, maintenance, proper operationsTo Prevent contamination or mix upTo Prevent contaminationFlow of materials  Layout17Lighting “Adequate lighting shall be provided in all areas.”(21CFR 211.44)Typical Lighting RequirementsAreaIllumination requirements(foot candles at work level)WarehouseDock space HallwaysLaboratoriesLibrary,Conference roomsBatching areaSolutions roomGarment roomAseptic suiteWashrooms, loungesCafeteriaOffices353535~5010010070~10070~10050100~15050~7030~7070~10018Schedule of minimum air requirements for various manufacturing spacesTypical roomsParticlecount(0.5m)Filter requiredTemperaturerange(°F)Humidity range(%)Pressure(inches of water)Air changes per hourWarehouse or equivalentPackagingCafeteriaOfficesLoungeLaboratory or equivalentManufacturing nonsterile productsManufacturing sterile productsWash area equipment product container/closuresGown roomFill-seal roomOver work surfaceNot defined DisposableNot defined Disposable 100,000 30-65% NIST 10,000 95% NIST -100,00010,000 HEPA 1,000-10,000 HEPA 100 HEPA 72  12 50  15 Not defined 72  5 50  15 Not defined 72  5 50  15 Not defined 72  5 50  20 Not defined 74  8 55  20 0.05 72  5 45 5 0.05 72  5 45 5 0.05 115-2015-2020-3020-3030-40Laminar300-40019Pre-treatment DistillationStorage DistributionSource waterChlorinationS S S SSSSLoop SystemPumpHolding Tank 80°C1. Filtration Sand Filter Charcoal Filter Cartridge Filter2. Primary Water Treatment Water Softener Deionizer Reverse Osmosis*s: samplingSWater For Injection(WFI) System20 Equipment21Design, Size & Location Appropriate DesignAdequate Size Suitable LocationFor CleaningFor Intended useFor MaintenanceConstruction22Cleaning & Maintenance At appropriate intervalsEquipment and utensils shall be cleaned and maintained SOP(Standard Operating Procedures)Assignment of responsibilityMaintenance & cleaning scheduleMethods, equipment & materialsRemoval of previous batch identificationProtection of clean equipment from contamination prior to useInspection of