laboratory design - parenteral drug association · pdf fileedited by scott sutton laboratory...

Edited by Scott Sutton

LABORATORYDESIGN

ESTABLISHING THEFACILITY AND

MANAGEMENTSTRUCTURE

CONTENTS

1 The Role of Microbiology in a PharmaceuticalQuality Program

Anthony M. CundellIntroductionMicrobiological Testing LaboratoriesThe Role of Microbiology in Quality Assurance/Control

USP Chapter <51> Antimicrobial Effectiveness TestUSP Chapter <61> and <62> Microbiological

Examination TestsUSP Informational Chapter <111>USP <71> Sterility TestUSP <85> Bacterial Endotoxin TestsUSP <1116> Microbiological Evaluations of Clean RoomsUSP <1231>Water for Pharmaceutical Purposes

Organization of the Microbiological Testing LaboratorybyWork Stations

Compliance in the Pharmaceutical Microbiology LaboratoryInvestigationsReferencesAbout the Author

1

Contents:Layout 1 3/6/10 14:01 Page 1

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2 Management Issues in the Microbiology Laboratory 13Roger Dabbah

IntroductionGeneral Principles of Management for the Microbiology

Function in an Organization 14The principle of accountability 14The principle of responsibility 14The principle of resource availability 14The principle of system thinking 15The principle of the management of people 15The principle of scanning the external environment 15The principle of open communication with supervisors,

peers, and employees 15The principle of ethical behavior 16

Technical Issues in a Microbiology Laboratory that Influencethe Management Issues 16Selection of methods to be used for microbiological

testing 16The methods used should be validated for their

intended purpose 17Technology transfer of methods from the microbiology

laboratory to plant QC laboratories 17USP tests — use and misuse 18Harmonization of Microbiological Tests and Requirements 18GMPs and GLPs impact on the management of a

microbiology laboratory 19ISO certification of a microbiology laboratory 20

Administrative Issues 21Performance plans for microbiologists 21Performance appraisal 21Performance criteria 22Hiring and firing of microbiologists 23Training of microbiologists 23

Managerial Issues in the Microbiology Function 24Planning 24

Is the activity routine or strategic? 25Describe the activity 26When was the activity started and why? 26When do you think the activity will be finished? 26What is the benefit of the activity for the

organization as a whole? 27What will happen if the activity is eliminated? 27What is the probability of success of that activity? 27

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What is the probability of success of that activity? 28What amount of resources does the activity require? 28Can you divide the activity into a minimum activity

and some incremental activities? 28Can the activity at any level be outsourced? 29

Organizing 29Monitoring and control 30Productivity 31Conflict management 31Budget development 32Relationship between the microbiology function and the

other functions of the organization 32Communications 32

Communications with scientific personnel 33Communications with support personnel 33

Out-Sourcing and/or Sub-contracting 34External Issues Confronted by the Management of the

Microbiology laboratory 34Professional associations 34Trade associations 35Standard-setting organizations 35Presentations at meetings 35Publications 36Regulatory agencies development related to microbiology

and microbiological quality assurance and control 36The Application of the Principles of Project Management in a

Microbiology function 37Planning 37

The development of a work breakdownstructure (WBS) 37

The development of a budget 37The development of a responsibility matrix 38

The project manager’s function 38The project team 38The project plan 38

Project scope 38Project objectives 39Technical approach to be used 39Specifications of final deliverable 39Schedule 39Budget 39Risk assessment 40Monitoring and control methods 40

Contents 3



Some Final Thoughts on the Management of Microbiology 40References 41About the Author 41

3 Quality Systems for the QC Microbiology Laboratory 43Lucia Clontz

Introduction 43The Cost of Quality 44Quality Systems 45

Implementing an effective quality system 46Design phase 47Implementation phase 47Verification phase 47Finalization phase 47Monitoring/revising phase 48

Quality System for the QC Microbiology Laboratory 48Management responsibilities 49

Leadership 49Meeting customer needs 49Commitment to continuous improvement 49

Resources 50Laboratory facilities 50Laboratory equipment 52Personnel 53Materials and supplies 54

Laboratory operations 59Documentation practices 60Laboratory investigations 60Monitoring operational inputs and outputs 62Change control 62Method suitability verification and validation 63Method transfer 69

Data analysis 70Variability in microbial counts 71Data trending and statistical analysis 72Alert and action levels 72

Conclusion 73References 73About the Author

4 Laboratory Investigations of Microbiological DataDeviations (MDD) 77

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Scott SuttonIntroduction 73Conducting a Laboratory Investigation 80

Equipment issues 85Media issues 85Microbial culture issues 86Personnel issues 86Procedural issues 87Sample issues 87

Closing the Laboratory Investigation 87Does the MDD Involve Finished Product Specification? 88Investigation MDD of Specific Tests 88

Antimicrobial efficacy tests 89Bacterial endotoxin tests 89Environmental monitoring events 90In-process tests — raw material and pre-sterilized

bulk bioburden 91Media fill events 91Microbial limits tests 92Sterility tests 92Water systems testing 93

Corrective Action Plan 93Futher Reading 94About the Author 95

5 Training Personnel in the Microbiology Laboratory 00Michele M. Conway

IntroductionTraining MethodsEvaluating TrainingOngoing TrainingLaboratory Specific TrainingSummaryReferencesAbout the Author

6 Safety Considerations in the Quality ControlMicrobiology Laboratory 00

Scott SuttonGeneral Safety Considerations

Contents 5



Biosafety ConsiderationsGeneral issuesBiological risk levelsBiological safety levelsLeadership

The Biological Safety CabinetClean BenchesHEPA Filtration of AirCleaning and Sanitization of a BSC

Standard Operating Procedures (SOP) Support— Recommended Instruction to the Technician

BiosafetyBiosafety manualBiohazardous spillsDecontamination of microorganismEating, drinking smoking, and the applicationof makeup in the labLaboratory hygiene proceduresTransferring culturesUse of PPEClean benches and biosafety hoodsShipping infectious materials

General SafetySummaryReferencesAbout the Author

7 Microbiological Quality for the 21st Century 00Linda Skowronsky

Introduction 00A Brief Historical ViewBeyond cGMPsQbD for Microbiology —The Microbiological Risk AssessmentTarget the Product ProfileIdentify the Critical Quality Attributes (CQAs)Linking Material Attributes and Process Parameters to

Drug Product CQAsFinished product and raw material limit strategiesTest method strategiesPreservative strategyStability strategy

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In-process control strategyEnvironment, process water, and cleaning strategies

Microbiologibal Control StrategyManage Product Lifecycle, Including Continual ImprovementTechnology TransferTest Method TransferMicrobiological Control Development ReportChange Control/Change Management — GeneralChanges that can Impact the Microbial Bioburden

of a FormulaConclusionReferencesAppendixAbout the Author

8 Design and Layout of the Microbiology Lab 00William M. Bennett

IntroductionPlanning

Building sitePublic utilities

User Requirements SpecificationBuilding siteLaboratoryEquipment list

Functional DesignUnitary operation diagramInteraction diagramRoom design criteriaPoint of use

Construction documentsArchitectural drawingsMechanical drawingsElectrical drawings

ConclusionReferencesAppendix A — URS DevelopmentAppendix B — Room Design CriteriaAbout the Author

Contents 7



9 Building and Equipping a Microbiology Laboratory:How to Budget Size and Cost 00

Bob Ferer and Scott SuttonIntroductionKnowYour ProcessNon-Routine TestingEquipment NeedsCommon Equipment NeedsStorage NeedsQuantify the Number of SamplesQuantify the Number of Samples for Stability and RetainContract Laboratory SupportCosts

Equipment costsFacility finishing costsAlternate calculation method

About the Authors

10 LaboratoryWater 00T.C.Soli

IntroductionDetermining the RequiredWater Quality

General lab operation requirementsMicrobiology lab operation requirements

Facility housekeepingEquipment and labware cleaningGrowth media preparationGeneral assay reagent preparationSpecial methodologies

System Design and Distribution ConsiderationsShared vs. dedicated systems

Extension of manufacturing water systemto laboratoriesCross-connection of the manufacturing andlaboratory systemsDedicated laboratory systems

Cost considerationCost/budget overruns

Optimizing water availability costsSystem qualification needsSource water impact

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Maintaining and monitoring qualityWhose job is it?Water system monitoring

Chemical qualityMicrobiological quailtyOther attributes of importanceEstablishing specificationsEstablishing alert and action levels

Impact of PoorWater QualityImpact on analyses and productsImpact on laboratory complianceImpact on facility compliance

Concluding SummaryReferencesAbout the Author

11 The Media Kitchen: Preparation andTesting ofMicrobiological Culture Media 00

Tim SandleIntroductionCulture Media

Complex culture mediaEnriched mediaDefined culture mediaSelective media

Design of the Media KitchenDesign of the facilitiesUtilitiesWaterSteam quality and autoclave operation

Incoming MaterialsMedia Manufacturing

Batch recordsEquipmentWeighingPreparation

Initial preparationRehydration

SterilizationAddition of supplementsFilling

Labelling

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Secondary SterilizationMedia Quarantine and Release

QuarantineRelease

Physical characteristicspHContamination/realityGel strengthGrowth promotion

Qualitative techniquesQuantitative techniquesQuality control of purchased media and reduced

testingStorage and ExpiryDisposalDocumentationTroubleshootingConclusionReferencesAbout the Author

12 Environmental Monitoring of Microbiology Laboratories 00Frank Settineri

IntroductionTrainingLaboratory Design and Flow

Sample receipt areaSample staging and holding areaBiohazard waste areaMedia preparation areasGeneral testing areaLive organism area (for identification, growth promotion,

and culture preparationCleanroom areas (suites or isolators) for sterility

testingDocumentationStandard Operating Procedures (SOPs)

ProtocolsReporting of data

Sample numberRaw data formSpecifications

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Equipment, Utensils, Instruments, andWork SurfacesAlert/Action LevelsNonviable ParticlesContract LaboratoriesObjectionable OrganismsSummaryReferencesAbout the Author

13 The Laboratory Design and Layout for MicrobialIdentification 00

Anthony M. CundellIntroductionInstrument Specifications

Instrument dimensions and weightTemperature and humidity requirementsAir handlingUV irradiationVibration controlsElectromagnetic field controlsCompressed gases or vacuum requirementsSolvent storagePower supply

Safety considerationsBiosafety Level 1Biosafety Level 2

ReferencesAbout the Author

14 Microbiology Manufacturing Support Laboratory 00David A. Porter

OverviewTypes of support testingEquipment, in generalFacilities, in general

DisinfectancyAntimicrobial EffectivenessBioburdenIdentificationSterility

Contents 11



Environmental MonitoringGeneral Equipment and FacilitiesReferencesAbout the Author

15 Building or Remodeling a Laboratory for theBacterial EndotoxinTest 00

Karen Zink McCulloughYour Constraints: Timelines and Budgets

TimelinesBudgets

User Requirements and SpecificationsWhat assays are you doing?What equipment do we need to perform these tasks?What utilities and provision for information technology

(IT) do you need?What furniture or finishes are required?What kind of floor plan do you need to accommodate

sufficient workspace, proper flows, convenientsupport areas, etc.?Lab spaceSupport areasOffice space

Create and Execute aValidation Master PlanStandard Operating Procedures and TrainingSummaryReferencesAbout the Author

Laboratory Design12



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