Environmental Monitoring And Contamination Control .

Environmental Monitoring and Contamination ControlPharMEDium Lunch and Learn SeriesLUNCH AND LEARNEnvironmental Monitoring and Contamination ControlSeptember 11, 2015Featured Speaker: Scott Sutton, Ph.D.The Microbiology NetworkN. Chili, New York1CE Activity Information & AccreditationProCE, Inc. (Pharmacist and Tech CE)1.0 contact hourFunding:g This activityy is self‐funded throughgPharMEDium.It is the policy of ProCE, Inc. to ensure balance, independence, objectivity and scientific rigor in all of its continuingeducation activities. Faculty must disclose to participants the existence of any significant financial interest or any otherrelationship with the manufacturer of any commercial product(s) discussed in an educational presentation. Dr. Suttonhas no relevant commercial and/or financial relationships to disclose.2ProCE, Inc.www.ProCE.com1

Environmental Monitoring and Contamination ControlPharMEDium Lunch and Learn SeriesOnline Evaluation, Self-Assessmentand CE Credit Submission of an online selfself‐assessmentassessment and evaluation is theonly way to obtain CE credit for this webinar Go to www.ProCE.com/PharMEDiumRx Print your CE Statement online Live CE Deadline: October 9, 2015 CPE Monitor– CE information automatically uploaded to NABP/CPE Monitor within 1to 2 weeks of the completion of the self‐assessment and evaluationEvent CodeCode will be provided at the end of today’s activityEvent Code not needed for On‐Demand3Ask a Question Submit your questions to your site manager. Questions will be answered at the end of thepresentation.Your question. . . ?4ProCE, Inc.www.ProCE.com2

Environmental Monitoring and Contamination ControlPharMEDium Lunch and Learn SeriesResources Visit www.ProCE.com/PharMEDiumRx to access:– Handouts– Activity information– Upcoming live webinar dates– Links to receive CE credit5Environmental Monitoring andContamination ControlScott Sutton, PhDscott.sutton@microbiologynetwork.comSeptember 11, 20156ProCE, Inc.www.ProCE.com3

Environmental Monitoring and Contamination ControlPharMEDium Lunch and Learn SeriesDisclaimer I am an independent consultant.I have been involved with USP for many years.I do not represent USP or any other organization.Opinions expressed in this webinar are minealone, and should not be interpreted as thepolicies, positions or whims of any otherorganization.7 2015 Microbiology Network, Inc.Presentation Overview What’s the Point of the Program?CComponentst off theth ProgramPAppropriate Sites for MonitoringWhat Are We Supposed to Do With Allthe Data?8 2015 Microbiology Network, Inc.ProCE, Inc.www.ProCE.com4

Environmental Monitoring and Contamination ControlPharMEDium Lunch and Learn SeriesContamination ControlControlCleaning/Sanitization- Facility- ter MonitoringAir MonitoringSurface MonitoringPersonnelPhysical BarriersWater SanitizationRaw Material andin-processinprocessMonitoringFinished ProductTesting9Sutton, S. 20015. Bioburden Contaminnation Control: AHolistic Overrview. Amer Pharm Rev In Press 2015 Microbiology Network, Inc.10 2015 Microbiology Network, Inc.ProCE, Inc.www.ProCE.com5

Environmental Monitoring and Contamination ControlPharMEDium Lunch and Learn SeriesWhat is the Point of the Program?USP 797 “The ES program should provide information tostaff and leadership to demonstrate that the PEC ismaintaining an environment within thecompounding area that consistently ensuresacceptably low viable and nonviable particle levels.”11 2015 Microbiology Network, Inc.What is the Point of the Program?USP 797 “Environmental sampling shall occur as part of a comprehensive qualitymanagement program and shall occur minimally under any of thefollowing conditions: as part of the commissioning and certification of new facilities andequipment; following any servicing of facilities and equipment;This section of 797 is as part of the re-certification of facilities and equipment (i.e.,commonly interpreted as every 6 months);“every six months” in response to identified problems with end products or staff technique; or in response to issues with CSPs, observed compounding personnelwork practices, or patient-related infections (where the CSP is beingconsidered as a potential source of the infection).”12 2015 Microbiology Network, Inc.ProCE, Inc.www.ProCE.com6

Environmental Monitoring and Contamination ControlPharMEDium Lunch and Learn SeriesWhat’s the Point?Demonstration of Microbial Control Sanitization Studies Contamination control planning Equipment Hold time Studies (establishment of cleanand dirty hold times - process hold times are processspecific) Selection of sample sites for environmentalmonitoring. EstablishmentE t bli ht off pharmacy-relevanthlt alertl t andd actiontilevels for controlled environments Ongoing Monitoring Program13 2015 Microbiology Network, Inc.FDA 483 Observations162 483 reports on fda.govAccessed 9/2/1514 2015 Microbiology Network, Inc.ProCE, Inc.www.ProCE.com7

Environmental Monitoring and Contamination ControlPharMEDium Lunch and Learn SeriesTopics of FDAPharmacy 483ObservationsEnvironmentalgMonitoring15 2015 Microbiology Network, Inc.EM – Documentation of PharmacyEnvironment “State of Control”"In aseptic processing, one of the most important laboratorycontrols is the environmental monitoring programprogram. Thisprogram provides meaningful information on the quality ofthe aseptic processing environment (e.g., when a givenbatch is being manufactured) as well as environmentaltrends of ancillary clean areas. Environmental monitoringshould promptly identify potential routes of contamination,allowing for implementation of corrections before productcontamination occurs (211.42 and 211.113)."FDA. 2004. Guidance for Industry: Sterile Drug Products Produced by AsepticProcessing - Current Good Manufacturing Practice. Section X.A.1.16 2015 Microbiology Network, Inc.ProCE, Inc.www.ProCE.com8

Environmental Monitoring and Contamination ControlPharMEDium Lunch and Learn SeriesEM – Documentation ofFacility State of Control"Environmental monitoring data will provideinformation on the quality of the manufacturingenvironment.“ FDA. 2004. Guidance for Industry: Sterile DrugProducts Produced by Aseptic Processing - Current Good ManufacturingPractice. Section X.A.2.USP 797 “TheThe ES program should provide information to staff and leadership todemonstrate that the PEC is maintaining an environment within thecompounding area that consistently ensures acceptably low viable andnonviable particle levels.”17 2015 Microbiology Network, Inc.FDA 503B CGMP Draft Guidance “Sterile drugs should be produced only in ISO 5or better air quality.” “The air cleanliness classification of the areasurrounding the ISO 5 zone immediately adjacentto the aseptic processing line should meet, at aminimum, ISO 7 (Class 10,000) standards.”Guidance for Industry: Current Good Manufacturing Practice — Interim Guidance for Human DrugCompounding Outsourcing Facilities Under Section 503B of the FD&C Act July, 2014Section III.A. Facility Design18 2015 Microbiology Network, Inc.ProCE, Inc.www.ProCE.com9

Environmental Monitoring and Contamination ControlPharMEDium Lunch and Learn SeriesFDA 503B CGMP Draft Guidance Cites 21 CFR 211.42(c)(10)(iv) for EM program Expectations: Cover all production shifts and include monitoring during normal productionconditions Include at least daily monitoring of the ISO 5 zone during operations Establish alert and action limits and appropriate responses to each Describe use of sampling devices, alert and action limits, and testing methods(e.g., media, plate exposure times, incubation times and temperatures) thatare designed to detect environmental contaminants, including changes inmicroflora type and amount Be supported by an evaluation of the choice of the sampling locations andsampling methodsGuidance for Industry: Current Good Manufacturing Practice — Interim Guidance for Human DrugCompounding Outsourcing Facilities Under Section 503B of the FD&C Act July, 2014Section III.C. Environmental and Personnel Monitoring19 2015 Microbiology Network, Inc.FDA 503B CGMP Draft Guidance Cites 21 211.113(b) and 211.28(a) for PersonnelMonitoringp Expectations: Includes a routine program for daily/shift monitoring of operators’ gloves andan appropriate schedule for monitoring gowns during operations Establishes limits that are based on the criticality of the operation relative tothe contamination risk to the product Calls for an investigation of results that exceed the established levels ordemonstrate an adverse trend, a determination of the impact on the sterilityassurance of finished products intended to be sterile, and the developmentand execution of appropriate corrective actionsGuidance for Industry: Current Good Manufacturing Practice — Interim Guidance for Human DrugCompounding Outsourcing Facilities Under Section 503B of the FD&C Act July, 2014Section III.C. Environmental and Personnel Monitoring20 2015 Microbiology Network, Inc.ProCE, Inc.www.ProCE.com10

Environmental Monitoring and Contamination ControlPharMEDium Lunch and Learn SeriesFDA 503B CGMP Draft GuidanceFinally, the draft guidance recommends laboratory QCmeasures:“Procedures should include establishing the validity of themicrobiological media, including the preparation,sterilization, and growth potential of the media used inperforming tests, including environmental and personnelgmonitoring.”Guidance for Industry: Current Good Manufacturing Practice — Interim Guidance for Human DrugCompounding Outsourcing Facilities Under Section 503B of the FD&C Act July, 2014Section III.C. Environmental and Personnel Monitoring21 2015 Microbiology Network, Inc.Presentation Overview What’s the Point of the Program?CComponentst off theth ProgramPAppropriate Sites for MonitoringWhat Are We Supposed to Do With Allthe Data?22 2015 Microbiology Network, Inc.ProCE, Inc.www.ProCE.com11

Environmental Monitoring and Contamination ControlPharMEDium Lunch and Learn SeriesMonitoring Program Components Written proceduresg of ppersonnelTrainingSurface monitoringMicrobial air monitoringNon-viable particulate air monitoringPersonnel monitoringCritical utilities-water, compressed gasses23 2015 Microbiology Network, Inc.Monitoring Program Components Surfaces Using sterile materials is appropriate, writtenprocedure should include sanitizationprocedures for all items taken into the asepticareas Monitor surfaces in critical and non-criticalareas SelectS l t sitesit thatth t indicatei di t effectivenessff tioffsanitization programs and appropriatepersonnel practices24 2015 Microbiology Network, Inc.ProCE, Inc.www.ProCE.com12

Environmental Monitoring and Contamination ControlPharMEDium Lunch and Learn SeriesMonitoring Program Components Typical surfaces monitored include: Floors, walls and ceilings Control panel surfaces Doors, especially push plates Equipment surfaces, both non-product contactand product contact surfacesContactCt t platesl tFlat Paddle SamplersSwabs25 2015 Microbiology Network, Inc.Monitoring Program Components Microbial air Sterile materials Disinfection of equipment Typical areas to monitor include: In the critical zones (ISO 5), near productexposure areas In the support/non-critical areas (ISO 7) basedon area usageActive Air SamplersPassive Sampling26 2015 Microbiology Network, Inc.ProCE, Inc.www.ProCE.com13

Environmental Monitoring and Contamination ControlPharMEDium Lunch and Learn SeriesMonitoring Program Components Non-viable particulate Disinfection of equipment Monitor in critical and non-critical areas Typical areas to monitor include: Same sites as microbial monitoring Additional sites in critical zones (ISO 5)27 2015 Microbiology Network, Inc.Utilities Water-usually limited number of sites in asepticareas Compressed gasses Product contact (purging or overlay) Equipment operation (exhausts into room)28 2015 Microbiology Network, Inc.ProCE, Inc.www.ProCE.com14