usp 797 pharmacy cleanrooms - facility ... - … 797 pharmacy cleanrooms - facility requirements...

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Copyright Technovation Systems, Inc. 2004, 2005,2006, 2007. Technovation System, Inc Proprietary Information

www.CleanroomSys.com

USP 797USP 797 Pharmacy Cleanrooms Pharmacy Cleanrooms -- Facility Requirements & Facility Requirements &

PlanningPlanning

Technovation Systems, Inc.Technovation Systems, Inc.804804--744744--06040604

[email protected]@technovation.org

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Technovation Systems, Inc. Technovation Systems, Inc. ––an Introductionan Introduction

A design/build engineering firm specializing in A design/build engineering firm specializing in cleanrooms for Life Sciences, Biotech, cleanrooms for Life Sciences, Biotech, Pharmaceutical and Hospital applications.Pharmaceutical and Hospital applications.A manufacturer of advanced energy efficient A manufacturer of advanced energy efficient filtration/air handling equipment.filtration/air handling equipment.R&D firm with expertise in contamination control, R&D firm with expertise in contamination control, particles science, fluid mechanics and engineering.particles science, fluid mechanics and engineering.

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Examples of Cleanroom ProjectsExamples of Cleanroom ProjectsWalter Reed Army Medical Center Walter Reed Army Medical Center –– USP 797 PharmaciesUSP 797 PharmaciesLIFENET LIFENET –– Tissue ProcessingTissue ProcessingPhilip Morris Philip Morris –– R&D LabsR&D LabsEncelleEncelle, Inc , Inc –– BiotechBiotechMedical College of VAMedical College of VA –– islet lab islet lab -- BiotechBiotechBurlington & Burlington & TriStateTriState –– Cleanroom LaundriesCleanroom LaundriesMed Med PharmexPharmex -- PharmaceuticalPharmaceuticalSchwarzSchwarz--PharmaPharma -- PharmaceuticalPharmaceuticalMSHA MSHA –– US Dept of Labor US Dept of Labor –– Test LabTest LabDow Chemical Dow Chemical –– Cleanroom Glove packagingCleanroom Glove packagingBeckman Coulter Beckman Coulter –– Medical DevicesMedical DevicesHollister Hollister –– Medical DevicesMedical DevicesUniversities of Athens & CreteUniversities of Athens & Crete –– BSL3 labs for 2004 OlympicsBSL3 labs for 2004 OlympicsJM Huber Corporation JM Huber Corporation –– Material Science LabsMaterial Science Labs

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Technological Innovation for Technological Innovation for CleanroomsCleanrooms

Advanced Energy Efficient Design Advanced Energy Efficient Design –– by means of by means of Technovation Technovation computer modelscomputer models and and advanced air advanced air handling technologyhandling technology..Low bio burden cleanroom technologies.Low bio burden cleanroom technologies.Expert DQ/IQ/OQ services for easier cGMP/ GTP/ Expert DQ/IQ/OQ services for easier cGMP/ GTP/ GxP compliance/USP 797 validation.GxP compliance/USP 797 validation.PMPM with multi disciplinary expertise with multi disciplinary expertise –– including including contamination controlcontamination control..Expertise in USP 797 ConformanceExpertise in USP 797 Conformance

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USP 797 USP 797 -- GuidelinesGuidelines

Current Status Current Status –– ISO 8 with anteroom and ISO ISO 8 with anteroom and ISO 5 work benches5 work benchesUSP 797 USP 797 –– Proposed Revisions (est. 2007), ISO Proposed Revisions (est. 2007), ISO 7 with ISO 8 (7 with ISO 8 (ISO 7 for Chemo & NuclearISO 7 for Chemo & Nuclear) ) anteroom and ISO 5 Zone/work benchesanteroom and ISO 5 Zone/work benches

Ref: Dr. Christina Lee, USPRef: Dr. Christina Lee, USPConclusion Conclusion –– Build for Proposed RevisionsBuild for Proposed Revisions

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USP 797USP 797-- GuidelinesGuidelines““Proposed RevisionsProposed Revisions””

ISO Class 5ISO Class 5 –– Compounded Sterile Products Compounded Sterile Products ““CSPCSP”” Work Work Area. Area.

ISO Class 7ISO Class 7 –– Outside CSP Work Area or Outside CSP Work Area or compounding roomcompounding room

-- CSP in general pharmacies requiresCSP in general pharmacies requirespositive pressure positive pressure

-- Negative pressure must be present for Negative pressure must be present for hazardous/potent materials i.e. Oncology/Nuclearhazardous/potent materials i.e. Oncology/Nuclear

ISO Class 7 (Chemo) or 8 (IV)ISO Class 7 (Chemo) or 8 (IV) -- Airlock/Gowning room Airlock/Gowning room for entry into cleanroomfor entry into cleanroom

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USP 797 New GuidelinesUSP 797 New Guidelines

Material passMaterial pass--thru into ISO Class 7thru into ISO Class 7Monitoring of temperature, humidity, and Monitoring of temperature, humidity, and pressure differentials is desirablepressure differentials is desirableSurfaces should be flush & Surfaces should be flush & sterilizablesterilizableProtocols for Personnel gowning, washing, Protocols for Personnel gowning, washing, etc.etc.

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USP 797 Revision USP 797 Revision ……....

ISO Class 5 Environment

The Class 5 Environment is to be located in a The Class 5 Environment is to be located in a Class 7 Room.Class 7 Room.Personnel must be fully gowned, covered and Personnel must be fully gowned, covered and gloved in the Class 7 area.gloved in the Class 7 area.

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USP 797 Revision USP 797 Revision ……..

ISO Class 7 EnvironmentPersonnel must be fully gowned, covered and Personnel must be fully gowned, covered and gloved.gloved.PassPass--thru or ISO 8thru or ISO 8-- anteroom must be used to anteroom must be used to access the area.access the area.No No stockstock can be stored in the area, but material to can be stored in the area, but material to be processed is allowable.be processed is allowable.Admixture jobs must be set up outside and Admixture jobs must be set up outside and transferred in through an airlock/passtransferred in through an airlock/pass--thru.thru.

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USP 797 Revision USP 797 Revision ……..Ante Room ISO Class 7 or 8Suitable for IV anteroom onlySuitable for IV anteroom only, not CSP, not CSPAll storage shelves on casters for All storage shelves on casters for removal removal –– cleaning/sterilization.cleaning/sterilization.Refrigeration is allowed in the area, but Refrigeration is allowed in the area, but passpass--thru refrigeration is preferredthru refrigeration is preferredComputers are allowed.Computers are allowed.

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Implied USP Bio Burden RequirementsImplied USP Bio Burden RequirementsClass 5 RequirementsClass 5 Requirements

AirAir 0.1 cfu/ft0.1 cfu/ft33

SurfaceSurface 3 3 cfucfu/plate/plate**

GownsGowns 5 5 cfucfu/plate/plateClass 7 RequirementsClass 7 Requirements

AirAir 0.5 0.5 cfucfu/ ft/ ft33

SurfaceSurface 5 5 cfucfu/plate/plateGownsGowns 10 10 cfucfu/plate/plate

Class 8 RequirementsClass 8 RequirementsAirAir 2.5 2.5 cfucfu/ ft/ ft33

SurfaceSurface 20 20 cfucfu/plate/plateGownsGowns 30 30 cfucfu/plate/plate

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A A ““CleanroomCleanroom”” is a Cleanroomis a Cleanroom………… only ifonly if

Particle, Bio Burden, Temperature, Humidity Particle, Bio Burden, Temperature, Humidity and Pressure are controlled and preferably, and Pressure are controlled and preferably, automatically monitored.automatically monitored.The Air Handling System is Critical to the The Air Handling System is Critical to the success of the Cleanroom. success of the Cleanroom. It is It is designed,designed, constructed constructed and and usedused in a manner in a manner to minimize the introduction, generation, and to minimize the introduction, generation, and retention of particles inside the room. retention of particles inside the room.

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Why a Dedicated Air Handling Why a Dedicated Air Handling System is a System is a ““MUSTMUST””

A Shared system A Shared system can not meetcan not meet the requirements the requirements becausebecause::Typically not enough air changes availableTypically not enough air changes availableLose control of the T, RH & PLose control of the T, RH & PYou may disperse Pharmacy chemicals/air You may disperse Pharmacy chemicals/air throughout the buildingthroughout the buildingFilters will be filtering more dirty air, less useful Filters will be filtering more dirty air, less useful life of life of HEPAHEPA’’ss

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TechnovationTechnovation’’s Solutions Solution

Contiguous Class 5 Environmental Zones Contiguous Class 5 Environmental Zones created in Class 7 Room.created in Class 7 Room.No Flow Benches are required.No Flow Benches are required.Bactericidal BioPlusBactericidal BioPlus®® HEPA Filters. HEPA Filters. Energy Efficient Design.Energy Efficient Design.No initial cost penalty.No initial cost penalty.

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TYPICAL IV PHARMACY

LAYOUT

15

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TYPICAL NUCLEAR/ONCOLOGY/ CHEMO PHARMACY LAYOUT

16

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Energy Efficient Design achieved Energy Efficient Design achieved via via ……..

Air Flow ModelingAir Flow Modeling –– 40% of operating costs are 40% of operating costs are due to airflow rates used due to airflow rates used –– hence this must be hence this must be optimized.optimized.ReRe--Heat MinimizationHeat Minimization –– Optimized Bypass Air Optimized Bypass Air Handling System Handling System –– saves up to 25% in operating saves up to 25% in operating costs.costs.BioPlusBioPlus®® HEPA In Duct filtersHEPA In Duct filters –– Ultra Low Ultra Low Pressure Drop (ULPD) and bactericidalPressure Drop (ULPD) and bactericidalResult = significant Cost savings vs. Result = significant Cost savings vs. Conventional AH SystemsConventional AH Systems

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Current Airflow Design Methods used by our competition… ChartsCharts recommending Av. Velocity/ Air Changes/hr (ACH) are used. These charts have no technical basis.

ISO Class

Velocity, fpm ACH

3 60-100 360-5404 50-90 300-5405 40-80 240-4806 25-40 150-2407 10-15 60-90

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Design VariablesDesign Variables• Airflow design

depends on many variables.

• Design charts do not take these variables into account.

• Technovation uses its proprietary Dilution and Transient Analysis Models in conjunction with CFD analysis for Optimum Airflow

Energy EfficientAirflow Design

ProcessContamination

Generation

Filter Efficiency

ParticleTransport

Rate

AirflowDistribution

ProcessSensitivity

Re-entrainment

PerformanceCriteria/Class

Makeup Air& Concentration

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Technovation’s Optimized Bypass Distributed Air Handling System

TechnovationTechnovation’’s Optimized Bypass s Optimized Bypass Distributed Air Handling System Distributed Air Handling System

ACIn duct fan units with primary ULPD™ HEPAs

Optional Bank of Terminal HEPA filters

makeup

Cleanroom Flow Schematic

•AC flow is a fraction of total flow

•Flow/ velocity independence

Patent Pending

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ReRe--Heat MinimizationHeat MinimizationThis is accomplished by varying (optimizing) the This is accomplished by varying (optimizing) the byby--pass flow and AC flow so that the pass flow and AC flow so that the dehumidification exit temperature from the AC dehumidification exit temperature from the AC unit is also what is required to overcome the unit is also what is required to overcome the sensible heat load due to the fans and the sensible heat load due to the fans and the process.process.Reheat then is only used for fine temperature Reheat then is only used for fine temperature control control –– thereby saving significant amount of thereby saving significant amount of energy. energy.

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TechnovationTechnovation’’s Operating Cost s Operating Cost Savings (2003 energy costs)Savings (2003 energy costs)

Distributed Air System vs. Conventional Air System in a Distributed Air System vs. Conventional Air System in a ISO 5/ ISO 7 Work Environment ISO 5/ ISO 7 Work Environment Pharmacy areas assumed to be 400 sq.ftPharmacy areas assumed to be 400 sq.ft

MidMid--AtlanticAtlantic

NortheastNortheast CACA

$10,345$10,345 $15,345$15,345 $17,283$17,283Savings/yr

* Data on file at Technovation Systems, Inc

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Bio Burden / Energy ImplicationsBio Burden / Energy Implications

EEFEEF bactericidal filters result in bactericidal filters result in significantly lower (negligible) bio burden.significantly lower (negligible) bio burden.

Pharmacies must achieve USP Standards Pharmacies must achieve USP Standards for maximum allowable airborne bio for maximum allowable airborne bio burden levels.burden levels.

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Ultra Low PD (ULPD) BioPlusUltra Low PD (ULPD) BioPlus®®HEPAsHEPAs

Technovation’s 1997 R&D 100 Award winning filters are used in our distributed air handling systems.

0.60.6”” WC @ 2400 scfm WC @ 2400 scfm –– 22’’x2x2’’x12x12”” deep! 40% lower pressure deep! 40% lower pressure drop than conventional HEPA.drop than conventional HEPA.~ 3 times higher dust holding capacity due to lower PD and ~ 3 times higher dust holding capacity due to lower PD and formation of formation of porous dust deposits porous dust deposits ––lower lower filter maintenance costs.filter maintenance costs.Estimated savings of Estimated savings of ~ $900 per year per ~ $900 per year per filter vs conventional HEPAs.filter vs conventional HEPAs.Used in central and Used in central and distributed air handling systems.distributed air handling systems.

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Electrically Enhanced Filtration (EEF)

Electrically EnhancedElectrically Enhanced Filtration Filtration (EEF)(EEF)

BioPlus® Filter

A 90-95% DOP filter is electrically enhanced to a 99.99% DOP.Additionally the filter becomes bactericidal!

Winner of 1997 R&D 100 Award

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Lab Results – Bactericidal Properties of EEF (Staph. Epi.)

Lab Results Lab Results –– Bactericidal Bactericidal Properties Properties of EEF (of EEF (StaphStaph. . EpiEpi.).)

control 4.00 1.00E+06 Baseline

control 4.00 1.02E+05 After 24 Hours

EEF 4.00 0.00E+00 100% KILLED

EEF 4.00 3.44E+02 99.93% KILLED

FILTER EXPOSURE TIME

AV.CFUs

COMMENT

control or EEF

hours #/sq inch

EEF 4.00 0.00E+00 100% KILLED

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Cleanroom w/ EEF - Bio-burdenCleanroom w/ EEF Cleanroom w/ EEF -- BioBio--burdenburdenDesign Class 1,000 11/14/99 11/30/99

Av. cfu/ft3 Av. cfu/ft3Device Testing 0 0

Coating 0 0.057Formulations 0 0

Device Manufacturing 0.170 0.113Refrigeration 0 0

Isolation 0.170 0.849Class 1,000 Av 0.057 0.170

Design Class 1,000 12/13/99 1/28/00Av. cfu/ft3 Av. cfu/ft3

Device Testing 0.000 0.000Coating 0.000 0.000

Formulations 0.000 0.000Device Manufacturing 0.000 0.000

Refrigeration 0.000 0.000Isolation 0.000 0.000

Class 1,000 Av 0.000 0.000

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Validation Related Services During Validation Related Services During Design/BuildDesign/Build

DQ DQ –– Design QualificationDesign QualificationIQ IQ –– Installation QualificationInstallation QualificationCommissioningCommissioningOQ OQ –– Operational QualificationOperational Qualification

This documentation becomes part of the Master This documentation becomes part of the Master Validation Plan. Validation Plan. This is not required by USP 797This is not required by USP 797however, it ehowever, it ensures high quality design and nsures high quality design and construction.construction.

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Process Integration & ConsultingProcess Integration & Consulting

Cleanroom design cannot be divorced from the process Cleanroom design cannot be divorced from the process / process equipment./ process equipment.Cleanroom equipment must be carefully selected Cleanroom equipment must be carefully selected ––Technovation provides consulting utilizing our R&D Technovation provides consulting utilizing our R&D facility. Examples freezers, refrigerators, filling facility. Examples freezers, refrigerators, filling machines etc.machines etc.Material /chemical compatibility is an important issue Material /chemical compatibility is an important issue for process integration.for process integration.

Technovation with its strong background in research & Technovation with its strong background in research & process contamination control is able to better provide process contamination control is able to better provide these services to the end user.these services to the end user.

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Technovation Project ManagementTechnovation Project Management

Establishment of proper Establishment of proper Cleanroom Construction Cleanroom Construction ProtocolsProtocols (CCP), will prevent major cost and time (CCP), will prevent major cost and time overruns. E.g. isolating dust sources and preventing overruns. E.g. isolating dust sources and preventing contamination of duct work; utilizing rigid controls contamination of duct work; utilizing rigid controls when doing dry wall is ridiculous. when doing dry wall is ridiculous. CCPs based on CCPs based on ““probabilityprobability”” (requires (requires contamination control expertise) rather than contamination control expertise) rather than ““possibilitiespossibilities””, will save dollars$$$. E.g. , will save dollars$$$. E.g. understanding migration of dust from outer areas; understanding migration of dust from outer areas; lower level CCPs are sufficient while applying wall lower level CCPs are sufficient while applying wall finishes / floors.finishes / floors.

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Successful Design/Build ServicesSuccessful Design/Build Services

This requires expertise in:This requires expertise in:Basic Engineering Basic Engineering –– mechanical, HVAC, structural, mechanical, HVAC, structural, electrical, plumbing, safety.electrical, plumbing, safety.Contamination Control Contamination Control –– aerosol science, associated aerosol science, associated instrumentation and fluid mechanics, process instrumentation and fluid mechanics, process integration.integration.Validation related activitiesValidation related activities–– DQ/IQ/OQ.DQ/IQ/OQ.

Further, the Designer must be capable of Further, the Designer must be capable of partneringpartnering with with End User to translate process requirements into design End User to translate process requirements into design specifications.specifications.

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Why Chose Technovation?Why Chose Technovation?USP 797 ExpertiseUSP 797 ExpertiseDesign/Built ~ 100 CleanroomsDesign/Built ~ 100 CleanroomsSpecialize in Cleanroom Environments onlySpecialize in Cleanroom Environments onlyDedicated TeamDedicated TeamFunctional LayoutFunctional LayoutEnergy Efficient and Functional Design Energy Efficient and Functional Design Bactericidal BioPlusBactericidal BioPlus®® HEPA filtersHEPA filtersExpert Design Build Services, DQ,IQ,OQExpert Design Build Services, DQ,IQ,OQ

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Statement of Customer SatisfactionStatement of Customer Satisfaction

Technovation prides itself in our record of Technovation prides itself in our record of 100% customer satisfaction 100% customer satisfaction as evidenced by the as evidenced by the amount of repeat business we have amount of repeat business we have achieved.achieved. References testifying to our References testifying to our unparallel record customer satisfaction are unparallel record customer satisfaction are available.available.

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Next Step Next Step –– Phase I Design Phase I Design Technovation Technovation will assist your Hospitalwill assist your Hospital in the in the assessment of your pharmacies USP 797 compliance assessment of your pharmacies USP 797 compliance and potential cost. and potential cost. Coordinate meeting with Pharmacists to develop Coordinate meeting with Pharmacists to develop design specifications.design specifications.Conduct field survey.Conduct field survey.Develop architectural and equipment layout.Develop architectural and equipment layout.Define utility requirements.Define utility requirements.Develop budget cost.Develop budget [email protected]@technovation.org or call 804or call 804--744744--06040604

usp 797 pharmacy cleanrooms - facility ... - … 797 pharmacy cleanrooms - facility requirements...

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