http://www.slideshare.net/rks19761/pharmaceutical-plant

1. Green Design as AppliedGreen Design as Applied
to cGMP Buildingsto cGMP Buildings
Presented to ISPE NJ Chapter DayPresented to ISPE NJ Chapter Day
June 17, 2009June 17, 2009
W. Bruce Eckman, PhDW. Bruce Eckman, PhD
WBE ConsultingWBE Consulting

2. 22
Green vs. cGMPGreen vs. cGMP
 Two great influences on the design of 21Two great influences on the design of 21stst
Century Pharma BuildingsCentury Pharma Buildings
 We will look at their differences &We will look at their differences &
similaritiessimilarities

3. 33
What is GMP?What is GMP?
GMP refers to the Good Manufacturing PracticeGMP refers to the Good Manufacturing Practice
Regulations promulgated by the US Food and DrugRegulations 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, andDrug, and Cosmetic Act (See Chapter IV for food, and
Chapter V, Subchapters A, B, C, D, and E for drugs andChapter 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 ofrequire that manufacturers, processors, and packagers of
drugs, medical devices, some food, and blood takedrugs, 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 qualitypure, and effective. GMP regulations require a quality
approach to manufacturing, enabling companies toapproach 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 GMPand errors… Failure of firms to comply with GMP
regulations can result in very serious consequencesregulations 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

4. 44
What is GMP?What is GMP?continuedcontinued
 GMP regulations address issues including recordkeeping,GMP regulations address issues including recordkeeping,
personnel qualifications, sanitation, cleanliness, equipmentpersonnel 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 toallowing each manufacturer to decide individually how to
best implement the necessary controls. This providesbest implement the necessary controls. This provides
much flexibility, but also requires that the manufacturermuch flexibility, but also requires that the manufacturer
interpret the requirements in a manner which makes senseinterpret the requirements in a manner which makes sense
for each individual business.for each 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 theystands 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 anddate in order to comply with the regulation. Systems and
equipment used to prevent contamination, mixups, andequipment used to prevent contamination, mixups, and
errors, which may have been "top-of-the-line" 20 yearserrors, 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.

5. 55
Green BuildingGreen Building
““An integrated framework of design,An integrated framework of design,
construction, operations, and demolitionconstruction, operations, and demolition
practices that encompass thepractices that encompass the
environmental, economic, and socialenvironmental, economic, and social
impacts of buildings.”impacts of buildings.”
Building practices recognizing theBuilding practices recognizing the
interdependence of the natural and builtinterdependence of the natural and built
environment and seek to minimize the useenvironment and seek to minimize the use
of energy, water, and other naturalof energy, water, and other natural
resources while providing a healthy andresources 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

6. 66
GREEN vs. cGMPGREEN vs. cGMP
GovernmentGovernment
RegulationRegulation
 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/

7. 77
GREEN vs. cGMPGREEN vs. cGMP
Architectural 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)

8. 88
GREEN vs. cGMPGREEN vs. cGMP
Architectural FeaturesArchitectural 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

9. 99
GREEN vs. cGMPGREEN vs. cGMP
Energy 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?

10. 1010
GREEN vs. cGMPGREEN vs. cGMP
Energy 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

11. 1111
GREEN vs. cGMPGREEN vs. cGMP
PlumbingPlumbing
ConsiderationsConsiderations
 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

12. 1212
GREEN vs. cGMPGREEN vs. cGMP
Aqueous BasedAqueous Based
UtilitiesUtilities
 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

13. 1313
GREEN vs. cGMPGREEN vs. cGMP
Microorganisms/LivingMicroorganisms/Living
ThingsThings
 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

14. 1414
GREEN vs. cGMPGREEN vs. cGMP
HVACHVAC
 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

15. 1515
GREEN vs. cGMPGREEN vs. cGMP
HVACHVAC
 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)

16. 1616
GREEN vs. cGMPGREEN vs. cGMP
Administrative/EngineeriAdministrative/Engineeri
ngng
 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

17. 1717
Green vs. cGMP
Common to Both
Successful Design/OperationSuccessful Design/Operation
 Establish a vision that embraces sustainable and/orEstablish 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/orDevelop a project budget that covers green and/or
cGMP building measures. Allocate contingenciescGMP building measures. Allocate contingencies
for additional research and analysis of specificfor 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 properSeek advice of a design professional with proper
building experience.building experience.

18. 1818
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 toSelect a design and construction team that is committed to
the project vision. Modify the RFQ/RFP selection process tothe project vision. Modify the RFQ/RFP selection process to
ensure the contractors have appropriate qualification toensure the contractors have appropriate qualification to
identify, select, and implement an integrated system ofidentify, 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 testingDevelop a project schedule that allows for systems testing
and commissioning/Qualification (GMP)and commissioning/Qualification (GMP)
 Develop contract plans and specifications to ensure that theDevelop 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

19. 1919
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 62-640
F to minimize
sweating
 Electropolishing of Stainless

20. 2020
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

21. 2121
Green Design-Green Design-
ProcessesProcessesCargill-Dow: Biodegradable PolymerCargill-Dow: Biodegradable Polymer
Dependency on Fossil Fuels- 25-55% less (compared to oil- basedDependency 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
ChromatographyChromatography
Steady 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

22. 2222
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)

23. 2323
Green Design-Green Design-
API ManufacturingAPI Manufacturing
Disposable EquipmentDisposable Equipment
 Good Green CharacteristicsGood Green Characteristics
 Saves cleaning/sanitizing chemical discharge and/or pure waterSaves cleaning/sanitizing chemical discharge and/or pure water
heatupheatup
 Not so Green CharacteristicsNot so Green Characteristics
 Disposable sensors/sample devices/vessels – may requireDisposable sensors/sample devices/vessels – may require
extensive decon before disposalextensive decon before 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

24. 2424
Green vs. cGMPGreen vs. cGMP
CONCLUSIONSCONCLUSIONS
 Green is possible in GMP facilities inGreen 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

25. 2525
Green and cGMPGreen and cGMP
Design of BuildingsDesign of Buildings
ReferencesReferences
 Green Building Basics- California Integrated WasteGreen 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 PrimerTai-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- UtahNelson,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