Green Design as Applied to cGMP Buildings

1
Green Design as Applied to cGMP Buildings

• Presented to ISPE NJ Chapter Day
• June 17, 2009
• W. Bruce Eckman, PhD
• WBE Consulting

2
Green vs. cGMP

• Two great influences on the design of 21st
  Century Pharma Buildings
• We will look at their differences similarities

3
What is GMP?

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

4
What is GMP?continued

• GMP regulations address issues including
  recordkeeping, personnel qualifications,
  sanitation, cleanliness, equipment verification,
  process validation, and complaint handling. Most
  GMP requirements are very general and open-ended,
  allowing each manufacturer to decide individually
  how to best implement the necessary controls.
  This provides much flexibility, but also requires
  that the manufacturer interpret the requirements
  in a manner which makes sense for each individual
  business.
• GMP is also sometimes referred to as "cGMP". The
  "c" stands for "current," reminding manufacturers
  that they must employ technologies and systems
  which are up-to-date in order to comply with the
  regulation. Systems and equipment used to prevent
  contamination, mixups, and errors, which may have
  been "top-of-the-line" 20 years ago, may be less
  than adequate by today's standards. 

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Green Building

• An integrated framework of design,
  construction, operations, and demolition
  practices that encompass the environmental,
  economic, and social impacts of buildings.
• Building practices recognizing the
  interdependence of the natural and built
  environment and seek to minimize the use of
  energy, water, and other natural resources while
  providing a healthy and productive indoor
  environment.

Nornes,David- Life cycle cost analysis (LCC) in
the United States Green Building Industry.
ibe.colostate.edu/projects/theses/nornes_summary.p
pt
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GREEN vs. cGMPGovernment Regulation

• Green
• Tax Credits
• Rebates
• Grants
• Some reference in Building Codes
• Platinum LEED 7 to capital costs
• Save 73/ft2 operating costs

• cGmp
• 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.reedconstru
ctiondata.com/articles/read/leed-certification_pri
mer/
7
GREEN vs. cGMPArchitectural 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)

• cGmp
• 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. cGMPArchitectural Features contd

• 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

• cGMP
• 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. cGMPEnergy Conservation

• cGMP
• NA- most functional rooms not on perimeter
• Same
• Generally in offices/support areas not
  research/production
• Qualified save even more?

• 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

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GREEN vs. cGMPEnergy Supply

• Green Building Design/cGMP Design
• Sufficient Electric, Cooling, Heating
• Reliability of Supply
• Normal operation
• Grid outage
• Reduced cost by Cogeneration
• Demand Response Programs
• On-site regeneration by renewable resources

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GREEN vs. cGMPPlumbing 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

• cGMP
• 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. cGMPAqueous Based Utilities

• Green
• Plant Steam (special
  treatment chemicals?)

• cGMP
• 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. cGMPMicroorganisms/Living Things

• Green
• NA
• Disinfectant
• Minncare (Peracetic Acid)
• UV light to kill germs-surface/HVAC

• cGMP
• 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. cGMPHVAC

• Green
• Minimal Air Changes/hr
• Large recycle
• Green applications in laboratories
• Fan VFDs

• cGMP
• 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 VFDs

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GREEN vs. cGMPHVAC

• Green
• BMS time management of airflows becoming more
  common
• Enthalpy Wheel
• IAQ Maintained by CO2Measurements

• cGMP
• 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. cGMPAdministrative/Engineering

• Green
• Write requirements into building specifications
• No universal effect
• Need decision about 4 years before building
  completion
• Stress local materials

• cGMP
• FDA may object if you specify lofty green goals
  dont 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/Operation
• Establish a vision that embraces sustainable
  and/or cGMP principles and an integrated design
  approach
• Develop a clear statement of the projects vision,
  goals, design criteria and priorities
• Develop a project budget that covers green and/or
  cGMP building measures. Allocate contingencies
  for additional research and analysis of specific
  options. Seek sponsorship or grant
  opportunities.
• Seek advice of a design professional with proper
  building experience.

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Green vs. cGMP Common to Both

• Successful design/operation (contd)
• Select a design and construction team that is
  committed to the project vision. Modify the
  RFQ/RFP selection process to ensure the
  contractors have appropriate qualification to
  identify, select, and implement an integrated
  system of green building measures (especially in
  cGMP)
• Develop a project schedule that allows for
  systems testing and commissioning/Qualification
  (GMP)
• Develop contract plans and specifications to
  ensure that the building design is at a suitable
  level of building performance
• Create effective incentives and oversight
• Train all personnel in operation maintenance of
  finishes equipment

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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- Processes

• Cargill-Dow Biodegradable Polymer
• Dependency on Fossil Fuels- 25-55 less
  (compared to oil- based polymer)
• Global warming gases 10- 78 less
• Dupont Sonora Polymer ( textile use)
• From glucose from corn starch
• Dependency on Fossil Fuels- 50 less
  (compared to oil-based polymer)
• PAT for drying
• Reduce energy 80
• Reduce off-specification product
• Chromatography
• Steady State Recycling (SSR)
• 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_file
  s/Braunegg_Bulk.pdf

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Green Design- API Manufacturing

• Begins at Development of Chemicals/Drug Products
• Minimize Solvent use/ less toxic if necessary
• Use better Catalysts (low temperature reactions)
• Switchable solvents (polar/nonpolar)
• Ionic Liquids( low temperature molten organic
  salts)
• Supercritical solvents ( Carbon Dioxide-
  polar/nonpolar)
• Waste- minimize or promote degradation
• Higher protein titer
• Less raw ingredients
• Less waste
• Synthetic Source can be greener than the natural
  source
• (easier to specify synthetic ingredients then
  deal with variation (eg. Biotech)

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Green Design- API Manufacturing

• Disposable Equipment
• Good Green Characteristics
• Saves cleaning/sanitizing chemical discharge
  and/or pure water heatup
• Not so Green Characteristics
• Disposable sensors/sample devices/vessels may
  require extensive decon before disposal
• Large volume of waste to be landfilled or
  incinerated
• Fabricated from petrochemicals
• Sanitizers Green Available
• Minncare ( H202/Peracetic Acid)
• Evacuate/Spray/Quarantine/Ventilate- 3 hours
• Formaldehyde
• Evacuate/Spray/Quarantine/Ventilate/Test- 3 days

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Green vs. cGMP CONCLUSIONS

• Green is possible in GMP facilities in limited
  doses
• Office/Administrative areas can be green
• Use of disposables is a growing non-green practice

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Green and cGMP Design of Buildings

• References
• Green Building Basics- California Integrated
  Waste Management Board- http//www.ciwmb.ca.gov/GR
  EENBUILDING/Basics.htm
• Tai-Lee, Oka LEED Certification Primer
  http//www.reedconstructiondata.com/articles/read/
  leed-certification-primer/
• Nelson,Craig Green Building Project Development-
  Utah Housing 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_file
  s/Braunegg_Bulk.pdf