Presentation on theme: "Microbiological Validation"— Presentation transcript:
1 Microbiological Validation Mark OldcorneWrexham Maelor Hospital
2 What 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
3 Action 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’
4 5 Pillars of GMP Premises People Processes Products Procedures Profit!!!
5 Overview Microbiological validation of Premises People environmental monitoringcleaning and disinfectionPeopleoperator broth transfer testshand cleaning and disinfection
6 Underpinned by Procedures OverviewProcessesprocess broth teststransfer spraying validationgassing processesProductssterility testsUnderpinned by Procedures(parametric release!)
7 Validation Master Plan Part ofQA programmeSite Master FileSchedulesMethodsResponsibilities
13 Microbiological Validation General Considerations 3 Incubation times5-7 daysbut must read after day 1Incubation temperaturesBacteria oCFungi 20-25oC
14 Microbiological Validation General Considerations 4 Sterile mediaAseptically prepared platesPre-incubationIrradiated platesless risk of false positivesgrowth characteristics alteredFertility assessment
15 Microbiological Validation General Considerations 5 Viable but non-culturable organisms (VBNC)Presence of non-recoverable organismsResults are RetrospectiveProspective releaseRetrospective release
16 Interpretation of Results Facilities managementInvestigational threshold (Alert limits)Action limitCountsID of Organismssource of organismconsequences of contaminationpresence of new organismsfailure of control measures
17 Trend analysis 1 Identify progressive and gross changes variables WorkspaceRoomProductOperator (not just aseptic processing)Operator – spraying in
18 Trend 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
19 Microbiological Environmental Methods Random MethodsSettle platesContact samplingFinger dabsOrganised MethodsActive air sampling*Assumptions*
20 Settle Plates method of collection sampling area sampling time positioningtrend analysisrepresentative samplelaminar air flow consideration0o, 45o and 90o
21 Surface Counts methods sampling area and location pickup efficiency Rodac PlatesSwabsProprietary systemssampling area and locationpickup efficiencyneutralisationpost sampling removal of mediaapplication pressurevalidation of disinfection processes
22 Finger Dabs sampling technique what does it assess? holes in gloves poor transfer disinfection
23 Active Air Sampling methods sampling efficiency - recovery rates impingementfiltrationsampling efficiency - recovery ratesparticle sizesampling methoddisruption of air flow - isokinetic probesquantitative comparisonaccessibilitysensitivity
24 Sterility Testing Ideal test? - product Test lacks sensitivity Retest only available under certain conditionsProspective vs retrospectiveAppropriate levels of controlSAL of testing process
25 Broth Transfer Testing 1 Process transfer testsworst case scenario>batch sizex3 initially6 monthly repeatOperator transfer testsUniversal Broth Transfer TestAdapted operator tests or process tests
26 Broth 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?
27 Conclusions 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
28 The 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……….