Green Design as Applied to Green Design as Applied to cGMP Buildings cGMP Buildings

Presented to ISPE NJ Chapter DayPresented to ISPE NJ Chapter DayJune 17, 2009June 17, 2009

W. Bruce Eckman, PhDW. Bruce Eckman, PhDWBE ConsultingWBE Consulting

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Green vs. cGMPGreen vs. cGMP Two great influences on the design of Two great influences on the design of

2121stst Century Pharma Buildings Century Pharma Buildings We will look at their differences & We will look at their differences &

similaritiessimilarities

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What is GMP?What is GMP? GMP refers to the Good Manufacturing Practice GMP refers to the Good Manufacturing Practice

Regulations promulgated by the US Food and Drug Regulations promulgated by the US Food and Drug Administration under the authority of the Federal Food, Administration under the authority of the Federal Food, Drug, and Cosmetic Act (See Chapter IV for food, and Drug, and Cosmetic Act (See Chapter IV for food, and Chapter V, Subchapters  A, B, C, D, and E for drugs and Chapter V, Subchapters  A, B, C, D, and E for drugs and devices.) These regulations, which have the force of law, devices.) These regulations, which have the force of law, require that manufacturers, processors, and packagers of require that manufacturers, processors, and packagers of drugs, medical devices, some food, and blood take drugs, medical devices, some food, and blood take proactive steps to ensure that their products are safe, proactive steps to ensure that their products are safe, pure, and effective. GMP regulations require a quality pure, and effective. GMP regulations require a quality approach to manufacturing, enabling companies to approach to manufacturing, enabling companies to minimize or eliminate instances of contamination, mixups, minimize or eliminate instances of contamination, mixups, and errors… Failure of firms to comply with GMP and errors… Failure of firms to comply with GMP regulations can result in very serious consequences regulations can result in very serious consequences including recall, seizure, fines, and jail time.including recall, seizure, fines, and jail time.

From www.ispe.orgFrom www.ispe.org

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What is GMP?What is GMP?continuedcontinued GMP regulations address issues including recordkeeping, GMP regulations address issues including recordkeeping,

personnel qualifications, sanitation, cleanliness, equipment personnel qualifications, sanitation, cleanliness, equipment verification, process validation, and complaint handling. verification, process validation, and complaint handling. Most GMP requirements are very general and open-ended, Most GMP requirements are very general and open-ended, allowing each manufacturer to decide individually how to allowing each manufacturer to decide individually how to best implement the necessary controls. This provides much best implement the necessary controls. This provides much flexibility, but also requires that the manufacturer interpret flexibility, but also requires that the manufacturer interpret the requirements in a manner which makes sense for each the requirements in a manner which makes sense for each individual business.individual business.

GMP is also sometimes referred to as "cGMP". The "c" GMP is also sometimes referred to as "cGMP". The "c" stands for "current," reminding manufacturers that they stands for "current," reminding manufacturers that they must employ technologies and systems which are up-to-must employ technologies and systems which are up-to-date in order to comply with the regulation. Systems and date in order to comply with the regulation. Systems and equipment used to prevent contamination, mixups, and equipment used to prevent contamination, mixups, and errors, which may have been "top-of-the-line" 20 years errors, which may have been "top-of-the-line" 20 years ago, may be less than adequate by today's standards. ago, may be less than adequate by today's standards. 

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Green BuildingGreen Building “ “An integrated framework of design, An integrated framework of design,

construction, operations, and demolition construction, operations, and demolition practices that encompass the practices that encompass the environmental, economic, and social environmental, economic, and social impacts of buildings.”impacts of buildings.”

Building practices recognizing the Building practices recognizing the interdependence of the natural and built interdependence of the natural and built environment and seek to minimize the use environment and seek to minimize the use of energy, water, and other natural of energy, water, and other natural resources while providing a healthy and resources while providing a healthy and productive indoor environment.”productive indoor environment.”

Nornes,David- Life cycle cost analysis (LCC) in the United States Green Building

Industry. ibe.colostate.edu/projects/theses/nornes_summary.ppt

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GREEN vs. cGMPGREEN vs. cGMPGovernment RegulationGovernment Regulation

Green Tax Credits Rebates Grants Some reference in

Building Codes Platinum LEED + 7%

to capital costs Save $73/ft2 operating

costs*

cGmpcGmp FDA Created in 1906 No government funds Small GMP regulations-

long history of interpretation by individual inspectors

Adds many multiples to base building cost

* Leed Certification Primer http://www.reedconstructiondata.com/articles/read/leed-certification_primer/

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GREEN vs. cGMPGREEN vs. cGMPArchitectural FeaturesArchitectural Features

Green Green disinfectants Light/white exterior

walls/roofs Avoid extra consumption

of energy/metal Avoid Solvent based Acoustic Ceiling tiles Green roof (vegetative

plantings with/with out greenhouses)

cGmpcGmp Cleanability/Sterilizability Gasketed Lights in Ceiling

Sloped tops of wall mounted panels

Epoxy painted floors/walls Hard drywall ceilings Avoid (Could Pollute

intake air with pollen, etc)

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GREEN vs. cGMPGREEN vs. cGMPArchitectural Features Architectural Features

cont’dcont’d Green High Recycled Content

Cardboard Glass Metal

Low off gassing materials (eg. carpet, paint)

Sustainable harvested material

Locally produced

Reusable pallets

Recyclable collection area

Avoid mold roof/wall etc

cGMPcGMP Material certificates for

product contact surfaces-traceable to mill- virgin material

Same (non gmp areas) avoid cGMP areas

Neutral Possible for base bldg

materials Good for cleanability/reuse

(no wood in cGMP areas) May be a problem- could

cause vermin or dirty air intake

SAME

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GREEN vs. cGMPGREEN vs. cGMPEnergy ConservationEnergy Conservation

Green Minimal Glass-east/west

exposure Lighting Systems

High efficiency fluorescent Motion sensors (shut off

when unoccupied) Dimmer Switches Local Task Lighting

Commissioned Building Saves 5% energy vs. Uncommissioned

cGMPcGMP NA- most functional

rooms not on perimeter Same Generally in

offices/support areas not research/production

Qualified save even more?

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GREEN vs. cGMPGREEN vs. cGMPEnergy SupplyEnergy Supply

Green Building Design/cGMP DesignGreen Building Design/cGMP Design Sufficient Electric, Cooling, HeatingSufficient Electric, Cooling, Heating Reliability of SupplyReliability of Supply Normal operationNormal operation Grid outageGrid outage Reduced cost by CogenerationReduced cost by Cogeneration Demand Response ProgramsDemand Response Programs On-site regeneration by renewable resourcesOn-site regeneration by renewable resources

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GREEN vs. cGMPGREEN vs. cGMPPlumbing ConsiderationsPlumbing Considerations

Green Dual System

Normal-potable water (drinking/cooking)

Recycled (Gray) – flush toilets/irrigation

Surface/rainwater containment (roof leaders to common point)

Fixtures Ultra-low flush toilets Low flow shower heads IR activated faucets Waterless urinals

cGMPcGMP Potable quality needed to

make high purity water May introduce contaminants

Avoid standing water may grow microorganisms

Lack of water volume may comprise cleanliness

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GREEN vs. cGMPGREEN vs. cGMPAqueous Based UtilitiesAqueous Based Utilities

Green Plant Steam

(special treatment chemicals?)

cGMPcGMP Plant Steam Clean steam (adds to inefficiency

by heat exchange and extra heat losses-longer total length)

Clean steam may sit idle- producing condensate- often send down drain requiring direct potable water cooling

Clean steam may lead to “greener” (more pure) humidification

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GREEN vs. cGMPGREEN vs. cGMPMicroorganisms/Living ThingsMicroorganisms/Living Things

Green NA

Disinfectant Minncare (Peracetic Acid)

UV light to kill germs-surface/HVAC

cGMPcGMP Kill by chemicals or steam

(BSL-3, BSL-4) Pyrogen Test

Once used rabbits Now LAL

Disinfectants Hydrogen Peroxide

Formaldehyde Not quantifiable enough to be

validated

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GREEN vs. cGMPGREEN vs. cGMPHVACHVAC

Green Minimal Air Changes/hr Large % recycle

Green applications in laboratories

Fan VFD’s

cGMPcGMP Large Air Change/hr Often once thru Large/special airflows

Laminar Flow Hood Biosafety Cabinet Isolator/Glove Box

Automatic Hood Sash height minimization safety & energy conscious

Fan VFD’s

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GREEN vs. cGMPGREEN vs. cGMPHVACHVAC

Green BMS time management of

airflows becoming more common

Enthalpy Wheel

IAQ Maintained by CO2Measurements

cGMPcGMP BMS time management

of airflows done if air classification not compromised

May Introduce unclean particles into air supply

NA to process areas (heat load, cleanliness)

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GREEN vs. cGMPGREEN vs. cGMPAdministrative/EngineeringAdministrative/Engineering

Green Write requirements into

building specifications

No universal effect

Need decision about 4 years before building completion

Stress local materials

cGMPcGMP FDA may object if you specify

lofty green goals & don’t meet them

Green Supply Chain (Add Cost, time)

Need to make green decisions early in development (7-11 years before sale to public)

Ship many material/finished products from overseas

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Green vs. cGMP Common to Both

Successful Design/OperationSuccessful Design/Operation Establish a vision that embraces sustainable and/or Establish a vision that embraces sustainable and/or

cGMP principles and an integrated design approachcGMP principles and an integrated design approach Develop a clear statement of the projects vision, Develop a clear statement of the projects vision,

goals, design criteria and prioritiesgoals, design criteria and priorities Develop a project budget that covers green and/or Develop a project budget that covers green and/or

cGMP building measures. Allocate contingencies cGMP building measures. Allocate contingencies for additional research and analysis of specific for additional research and analysis of specific options. Seek sponsorship or grant opportunities.options. Seek sponsorship or grant opportunities.

Seek advice of a design professional with proper Seek advice of a design professional with proper building experience.building experience.

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Green vs. cGMP Common to Both

Successful design/operation (cont’d)Successful design/operation (cont’d) Select a design and construction team that is committed to Select a design and construction team that is committed to

the project vision. Modify the RFQ/RFP selection process to the project vision. Modify the RFQ/RFP selection process to ensure the contractors have appropriate qualification to ensure the contractors have appropriate qualification to identify, select, and implement an integrated system of identify, select, and implement an integrated system of green building measures (especially in cGMP)green building measures (especially in cGMP)

Develop a project schedule that allows for systems testing Develop a project schedule that allows for systems testing and commissioning/Qualification (GMP)and commissioning/Qualification (GMP)

Develop contract plans and specifications to ensure that the Develop contract plans and specifications to ensure that the building design is at a suitable level of building performancebuilding design is at a suitable level of building performance

Create effective incentives and oversightCreate effective incentives and oversight Train all personnel in operation & maintenance of finishes & Train all personnel in operation & maintenance of finishes &

equipmentequipment

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Green vs. cGMP High Energy Operations

GREEN Try to minimize NA Use “green” refrigerant

NA -

Minimize- high energy & chemical disposal issue (pH, dissolved metals)

cGMP Supercritical Fluids Cryogenic Gases Large cold rooms/freezers

(possibly green) High temperature to

sterilize/depyrogenate Ambient temperature as low

as 62-640F to minimize sweating

Electropolishing of Stainless

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Green vs. cGMP Disposables (Solids/Liquids)

GREEN(Modifications) Limited-Unique to each operation

Attempt to recycle/reuse (firewater, lawn watering)

Attempt to use aqueous or supercritical gas (CO2 is carbon neutral)

Minimize Packaging Materials

cGMP Plastic Filters Plastic Vessels/Tubing Bunnysuits/hairnets/sticky mats Gloves from Isolators Drying dessicant

Off spec distillate RO Reject

Clean Steam Condensate CIP Fluids Solvents (sometimes organic)

Special packaging needed for cGMP

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Green Design- ProcessesGreen Design- ProcessesCargill-Dow: Biodegradable PolymerCargill-Dow: Biodegradable Polymer Dependency on Fossil Fuels- 25-55% less (compared to oil- based Dependency on Fossil Fuels- 25-55% less (compared to oil- based

polymer)polymer) Global warming gases 10- 78% lessGlobal warming gases 10- 78% less

Dupont: Sonora Polymer ( textile use)Dupont: Sonora Polymer ( textile use) From glucose from corn starchFrom glucose from corn starch Dependency on Fossil Fuels- 50% less (compared to oil-based polymer)Dependency on Fossil Fuels- 50% less (compared to oil-based polymer)PAT for dryingPAT for drying

Reduce energy 80%Reduce energy 80%Reduce off-specification productReduce off-specification product

ChromatographyChromatographySteady State Recycling (SSR)Steady State Recycling (SSR)Send unresolved fractions back to column inlet (for reprocessing)Send unresolved fractions back to column inlet (for reprocessing)

Braunegg, G., Horvat, P., Atlic, A., Bona, R., Hesse, P., Koller, M., Kutschera, C. – From Renewable Resources to Bulk Products: The Future is WHITE BIOTECHNOLOGY www.hdb.hr/bec2008/PDF_files/Braunegg_Bulk.pdf

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Green Design- API Manufacturing

Begins at Development of Chemicals/Drug ProductsBegins at Development of Chemicals/Drug Products Minimize Solvent use/ less toxic if necessaryMinimize Solvent use/ less toxic if necessary Use better Catalysts (low temperature reactions)Use better Catalysts (low temperature reactions) Switchable solvents (polar/nonpolar)Switchable solvents (polar/nonpolar) Ionic Liquids( low temperature molten organic salts)Ionic Liquids( low temperature molten organic salts) Supercritical solvents ( Carbon Dioxide- polar/nonpolar)Supercritical solvents ( Carbon Dioxide- polar/nonpolar) Waste- minimize or promote degradationWaste- minimize or promote degradation Higher protein titerHigher protein titer

Less raw ingredientsLess raw ingredients Less wasteLess waste

Synthetic Source can be greener than the natural sourceSynthetic Source can be greener than the natural source (easier to specify synthetic ingredients then deal with variation (eg. Biotech)(easier to specify synthetic ingredients then deal with variation (eg. Biotech)

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Green Design- Green Design- API ManufacturingAPI Manufacturing

Disposable EquipmentDisposable Equipment Good Green CharacteristicsGood Green Characteristics

Saves cleaning/sanitizing chemical discharge and/or pure water heatupSaves cleaning/sanitizing chemical discharge and/or pure water heatup

Not so Green CharacteristicsNot so Green Characteristics Disposable sensors/sample devices/vessels – may require extensive decon Disposable sensors/sample devices/vessels – may require extensive decon

before disposalbefore disposal Large volume of waste to be landfilled or incineratedLarge volume of waste to be landfilled or incinerated Fabricated from petrochemicalsFabricated from petrochemicals

Sanitizers Green AvailableSanitizers Green Available Minncare ( H202/Peracetic Acid)Minncare ( H202/Peracetic Acid)

Evacuate/Spray/Quarantine/Ventilate- 3 hoursEvacuate/Spray/Quarantine/Ventilate- 3 hours FormaldehydeFormaldehyde

Evacuate/Spray/Quarantine/Ventilate/Test- 3 daysEvacuate/Spray/Quarantine/Ventilate/Test- 3 days

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Green vs. cGMP Green vs. cGMP CONCLUSIONSCONCLUSIONS

Green is possible in GMP facilities in Green is possible in GMP facilities in limited doseslimited doses

Office/Administrative areas can be greenOffice/Administrative areas can be green

Use of disposables is a growing non-Use of disposables is a growing non-green practicegreen practice

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Green and cGMP Green and cGMP Design of BuildingsDesign of Buildings

ReferencesReferences

Green Building Basics- California Integrated Waste Green Building Basics- California Integrated Waste Management Board- Management Board- http;//www.ciwmb.ca.gov/GREENBUILDING/Basics.htmhttp;//www.ciwmb.ca.gov/GREENBUILDING/Basics.htm

Tai-Lee, Oka LEED Certification Primer Tai-Lee, Oka LEED Certification Primer http://www.reedconstructiondata.com/articles/read/leed-http://www.reedconstructiondata.com/articles/read/leed-certification-primer/certification-primer/

Nelson,Craig Green Building Project Development- Utah Nelson,Craig Green Building Project Development- Utah Housing Coalition Conference October 16, 2007 http: rcac.orgHousing Coalition Conference October 16, 2007 http: rcac.org

Braunegg, G., Horvat, P., Atlic, A., Bona, R., Hesse, P., Koller, M., Kutschera, C. – From Renewable Resources to Bulk Products: The Future is WHITE BIOTECHNOLOGY www.hdb.hr/bec2008/PDF_files/Braunegg_Bulk.pdf