Microbiology and Auditing - New Home Page - …

1 Microbiology and AuditingDon SingerASQ Northeast Pharmaceutical GMP/Quality Conference 2011 Through the eyes of a MicrobiologistMicrobiology Audit = Inspection / InvestigationSystematic Auditing Planning Right People Tools Appropriate ObjectivesAuditing approachCorporate design or policy Team IndependentPurposeQuality SystemsBuild robustness into your quality systemscGMPsTypes of audits with Evaluation of Microbiological control Contract manufacture Contract Microbiology laboratory Excipientmanufacturer Active ingredient manufacturer Combination of any of the above Internal manufacture or laboratoryQuality Systems Inspection Quality system Production system Laboratory controls system Materials system Packaging and labeling system Facilities and equipment systemMicrobiological Quality Risk Management Dosage form Laboratory tests Materials managementRisk by route of administrationLowHighParenteralTablet, CapsuleOphthalmicLiquid-filled capsulesWound topicalsTopical ointmentInhaled -MDII nhaled -DPII ntranasal solutionTopical creamNebulizer solutionOticOral solutions, suspensionsLab tests risk from impact of results HighLowSterility TestBacterial endotoxintestAntimicrobial Preservatives Effectiveness TestBiological assaysMicrobial enumeration and Specified microorganisms testsMicrobial identificationMedia growth promotionMaterials risk of contaminationHighLowAnimal or plant origin ( lactose)Synthetic origin ( povidone)Mineral origin ( Talc)Mineral origin ( dyes, aromatics) Semi-synthetic origin ( captisol, HPM)UnprocessedHighly processedSome bioburdenreductionprocessingClassificati onManufacturing processAudit ExpertiseWhat is a QC Microbiologist?

2 Knowledge Base :ScienceOrigin and GrowthControlMicrobiological ScienceOrigin and Growth Water (H2O) Nutrition (CHO, CHON, CHOOH, minerals, etc.) Presence or absence of components of air Other Growth Factors pH temperature osmotic conditions light Microbial Origin and Survival moderate to extreme environments solid to liquid dense to dilute atmosphere, humans and other living organisms (animals -vegetation), water, soilRole of a QC MicrobiologistDesign for microbiological controlMonitor to continuously evaluateControlHow to manipulate the environment Understand microbial growth limitations Determine how to reduce or eliminatemicrobial growth Understand dynamics of environment and microbiological growth / survivalUnderstand Thoroughly?Do you have the appropriate background and experience for microbiological investigation?If you do not, then partner with a MicrobiologistTools to Assist cGMPs, guidance docs, pharmacopeias Quality tools such asUseful Quality Tools Assessment checklist or survey (developed by your Microbiologist colleague)How does Risk fit Inspection decisions?

3 High risk on-site inspection mandatory Moderate risk questionnaire assessment or on-site inspection Low risk questionnaireProcess flow chartRelease of raw materialsFermentationCentrifugationChrom atographyBulk substanceFiltrationFinal packaged productExcipientsWaterMicronizationSepar ationDryingHydrationWaterSterile filtrationFillingandProcess analysisDetails of Process with Controls HACCP plan Perform a virtual HACCP analysis using tour, procedures and assessment survey Amount of detail depends on level of riskAudit Findings Template Same document format as Lead auditorOr Modified document for notes during auditFor efficiency and clarity. Agreed on format with Lead auditorObjectivesI perform an audit with these intended quality systems in place for microbiological level of knowledge and capabilities of audited if continuous improvement is part of cultureObjectives (cont.) if culture matches knowledge and perspective with client where adds a relationship based on respect, shared learning, communicationsRight People ParticipantsTo ensure that adequate and timely information is generated during an auditQuestions should be directed to the Microbiologist who has accountability and responsibility, and possibly to their staffAdditionally, communicate with operators, or validation scientists, if appropriate( for sterile operations)

4 Success or FailureThe results from an audit depend on the accuracy of informationA non-microbiologist should have effective access to someone who is educated in pharmaceutical microbiologyVirtual Audit with a Microbiology AuditorCriteria to Consider for Manufacturing Audits Excipientcontrol C of A, specs, QC testing, material storage, weighing Process flow containment, gowning Process equipment validation, cleaning, sterilization, microbial monitoring Process areas cleaning, sanitization, access control, gowning, gloves, microbial monitoring, classification qualification Source of water, water system control and monitoringCriteria to Consider for Manufacturing Audits Formulation excipientand component handling, bulk material handling, in-process sampling, hold time qualifications Dosage dependent manufacture controls ( mixing, drying, milling, compaction) Finish/fill operations sampling, cleaning, operator technique/intervention, controls ( filtration, sterilization, closure control), process qualification Finished product QC testing, stability testingCriteria to Consider for Laboratory Audits Organization and reporting structure Laboratory layout Sample tracking, storage Media control, made or purchased Supplies, reagents control Instrument control calib.

5 , PM Lab and instrument cleaning, disinfectionCriteria to Consider for Laboratory Audits Lab monitoring SOPs and their control Microbial identification process Exceeded limit or atypical result procedure Quality improvement program, measures Proficiency testing Test methodology Method suitability proceduresCriteria to Consider for API or ExcipientManufacture Audit Process flow and contributing factors ( intended use of compound, parenteralvs. non-sterile) Monitoring of process Origin and control of raw ingredients Water system control and monitoring Microbial monitoring of product