FDA cGMP检查 英文

FDA cGMP InspectionsPeking University 2005FDA Inspections Periodic (biennial) comprehensiveForeign Inspections by Country in FY 200414%Germany Italy 10%China 7%United KingdomCanada 7%France 5%Japan 5%SwitzerlandOthers 19%Foreign Inspection in FY 2004by Firm TypeDosage 27%Intermediates2%Micronizer1%FDA cGMPs for 21st CenturyInitiativeAnnounced 8/2002; objectives include:Encourage adoption of new technologiesFDA cGMPs for 21st CenturyInitiativeBased Approach to Manufacturing and RegulationPharmaceutical InspectoratePharmaceutical InspectorateFDA Review staff, Compliance Officers andPI candidates attended training modulesPharmaceutical InspectorateField Investigators (18) from across U.S.make up the Pharmaceutical InspectorateProcess Analytical TechnologyPAT is a system for designing, analyzingand controlling“real time”measurements of criticalSee FDA Guidance document on PATProcess Analytical TechnologyContinuous real time measurements ofProcess Analytical TechnologyA process is generally considered wellProcess ValidationProcess validation begins with process development and continues beyond “validation”batchesProcess Validation“Process Validation Requirements for DrugSystem InspectionsMost Common GMPDeficiencies by System–API/ Dosage Inspections for 2004/5quipment1%Laboratory19%“State of Control”Detailed inspection of a system so that thesystem for every product (profile) classQuality SystemQuality must be built into the processQuality is not tested into the productRole of Management in QSQuality System Responsibilities cGMPsReview and approval duties for:Product Quality Reviews (at least annually)Quality system (continued)Laboratory Control System Adequate lab facilities under the Quality Unit which isAdequately staffed laboratories (supervisory and benchLaboratory Control System Reference Standards (primary; secondary)Laboratory Control System Written procedure (SOP) covering out ofresults conducted in aLaboratory Control RecordsProduction SystemProduction system(continued) Adequate written procedures& practiceProduction system(continued) Deviations investigated and documentedProcess validation based on knowledge of process (scientific basis for identifying critical steps/criticalFacilities & Equipment SystemLocation, design, construction appropriate toFacilities & Equipment System Defined areas or other control systems toIncoming materials (id, quarantine)Facilities & Equipment Systemreactive productFacilities & Equipment SystemLubricants, heating fluids or coolants (notUtilitiesQualified and appropriately monitored; drawingsDesigned and constructed to preventWaterJustify quality of water used to achieve statedMaterials Systemquarantine, storage, handling, sampling, testingSystem to evaluate suppliers (critical materials)Materials Systemassociated manifolds, filling and discharge linesMaterials SystemStored in manner to prevent degradation,Packaging & Labeling System Written procedures for receipt, identification,LabelingPackaging/Labeling OperationsAPIs are Drug Substances FDA Food, Drug and Cosmetic Act definition ofdiagnosis, cure, mitigation, treatment orregulations as guidanceStill true (see next slide) , however, ICH Q7A provides guidance on the application of thosecGMPs to APIs)From current FDA Compliance Program 56002 for Drug Manufacturing Inspections:(This is the compliance program for FDA“The cGMP regulations are not direct requirements for manufacture of APIs…….but they are guidance for cGMP in API manufacture.”Current FDA Compliance Guide on Process validationFrom FDA Compliance Policy Guide “Process Validation Requirements for Drug Products and Active Pharmaceutical Ingredients CPG 7132c.08”; revision date 12 March 2004:Validation of manufacturing processes is a requirement of the Current Good Manufacturing Practice (cGMP) regulations for finished pharmaceuticals, and is considered an enforceable element of current good manufacturing practice for active pharmaceutical ingredients (APIs) under the broader statutory cGMP provisions of the FederalFood, Drug, and Cosmetic Act”.Differences API/ Dosage FormGMP controls tighter for later API stepsSimilarities APIs/Dosage Forms Require demonstrated knowledge ofGMP controls to assure safety, identity,Similarities include….Processes for specific products vary incomplexity (either API or dosage can involveMore Similarities…..Knowledge of process based on Process。