Presentation on theme: "Microbiological Validation"— Presentation transcript:
1Microbiological Validation Mark OldcorneWrexham Maelor Hospital
2What is Validation?The QA of any preparation activity is reliant on the satisfactory validation of the proceduresValidation should demonstrate that the overall process will reproducibly provide a product that complies with its specification
3Action of proving (and documenting) that something ‘works’ What is validation?Action of proving, in accordance with the principles of GMP, that any procedure, process, equipment, material, activity or system leads to the expected resultsAction of proving (and documenting) that something ‘works’
45 Pillars of GMP Premises People Processes Products Procedures Profit!!!
5Overview Microbiological validation of Premises People environmental monitoringcleaning and disinfectionPeopleoperator broth transfer testshand cleaning and disinfection
6Underpinned by Procedures OverviewProcessesprocess broth teststransfer spraying validationgassing processesProductssterility testsUnderpinned by Procedures(parametric release!)
7Validation Master Plan Part ofQA programmeSite Master FileSchedulesMethodsResponsibilities
13Microbiological Validation General Considerations 3 Incubation times5-7 daysbut must read after day 1Incubation temperaturesBacteria oCFungi 20-25oC
14Microbiological Validation General Considerations 4 Sterile mediaAseptically prepared platesPre-incubationIrradiated platesless risk of false positivesgrowth characteristics alteredFertility assessment
15Microbiological Validation General Considerations 5 Viable but non-culturable organisms (VBNC)Presence of non-recoverable organismsResults are RetrospectiveProspective releaseRetrospective release
16Interpretation of Results Facilities managementInvestigational threshold (Alert limits)Action limitCountsID of Organismssource of organismconsequences of contaminationpresence of new organismsfailure of control measures
17Trend analysis 1 Identify progressive and gross changes variables WorkspaceRoomProductOperator (not just aseptic processing)Operator – spraying in
18Trend Analysis 2 Methods available visualisation by charting and graphical methodsstatistical analysispopulation study softwareexception reportingfollow up of problemslimitation of variablesnumber of exceptions (investigational or action limits) used as a measure of cleanliness
19Microbiological Environmental Methods Random MethodsSettle platesContact samplingFinger dabsOrganised MethodsActive air sampling*Assumptions*
20Settle Plates method of collection sampling area sampling time positioningtrend analysisrepresentative samplelaminar air flow consideration0o, 45o and 90o
21Surface Counts methods sampling area and location pickup efficiency Rodac PlatesSwabsProprietary systemssampling area and locationpickup efficiencyneutralisationpost sampling removal of mediaapplication pressurevalidation of disinfection processes
22Finger Dabs sampling technique what does it assess? holes in gloves poor transfer disinfection
23Active Air Sampling methods sampling efficiency - recovery rates impingementfiltrationsampling efficiency - recovery ratesparticle sizesampling methoddisruption of air flow - isokinetic probesquantitative comparisonaccessibilitysensitivity
24Sterility Testing Ideal test? - product Test lacks sensitivity Retest only available under certain conditionsProspective vs retrospectiveAppropriate levels of controlSAL of testing process
25Broth Transfer Testing 1 Process transfer testsworst case scenario>batch sizex3 initially6 monthly repeatOperator transfer testsUniversal Broth Transfer TestAdapted operator tests or process tests
26Broth Transfer Tests 2 Ideal test? - QA of process Statistical considerations to reach AQL1 in 1000or 1 in 10,000Frequency?Sensitivity - do we challenge the test?
27Conclusions Microbiological validation indicates personnel involvement All microbiological validation methods have limitationsMicrobiological validation methods cannot be used in isolation and should be used holistically to gain a true picture of product assurance
28The future Where does the validation cult go? Next stage is validating the validationNext stage to that is validating the validation of the primary validation and so on……….