Green Design as Applied to

cGMP Buildings

Presented to ISPE NJ Chapter Day

June 17, 2009
W. Bruce Eckman, PhD
WBE Consulting

Green vs. cGMP

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

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

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-todate 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.
4

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.ppt

GREEN vs. cGMP

Government Regulation

Green
cGmp
FDA Created in 1906
Tax Credits
No government funds
Rebates
Small GMP regulationsGrants
long history of
Some reference in
interpretation by
Building Codes
individual inspectors
Platinum LEED + 7%
Adds many multiples to
to capital costs
base
building
cost
2
Save $73/ft operating
* Leed Certification Primer
6
costs*http://www.reedconstructiondata.com/articles/read/leed-certification_primer/

GREEN vs. cGMP

Architectural 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)
7

GREEN vs. cGMP

Architectural Features
contd cGMP
Green
High Recycled Content

Material certificates for

Cardboard
product contact surfaces Glass
traceable to mill- virgin
Metal
material
Low off gassing materials (eg. Same (non gmp areas) avoid
carpet, paint)
cGMP areas
Sustainable harvested
Neutral
material
Possible for base bldg
Locally produced
materials
Good for cleanability/reuse
(no wood in cGMP areas)
Reusable pallets
May be a problem- could
cause vermin or dirty air
Recyclable collection area
intake
8

SAME

GREEN vs. cGMP

Energy Conservation
cGMP
Green
Minimal Glass-east/west NA- most functional
exposure
rooms not on perimeter
Lighting Systems
Same
High efficiency fluorescent
Generally in
Motion sensors (shut off
offices/support areas not
when unoccupied)
research/production
Dimmer Switches
Local Task Lighting
Commissioned Building
Saves 5% energy vs.
Uncommissioned

Qualified save even

more?

GREEN vs. cGMP

Energy 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
10

GREEN vs. cGMP

Plumbing Considerations
Green
Dual System
Normal-potable water
(drinking/cooking)
Recycled (Gray) flush
toilets/irrigation

cGMP
Potable quality needed to
make high purity water
May introduce contaminants

Surface/rainwater containment Avoid standing water may

grow microorganisms
(roof leaders to common point)
Fixtures
Ultra-low flush toilets
Lack of water volume may
Low flow shower heads
comprise cleanliness
IR activated faucets
Waterless urinals

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GREEN vs. cGMP

Aqueous 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 idleproducing condensateoften send down drain requiring
direct potable water cooling
Clean steam may lead to greener
(more pure) humidification
12

GREEN vs. cGMP

Microorganisms/Living
Things
Green

NA

cGMP
Kill by chemicals or steam
(BSL-3, BSL-4)
Pyrogen Test
Once used rabbits
Now LAL

Disinfectant
Minncare (Peracetic Acid)

UV light to kill germssurface/HVAC

Disinfectants
Hydrogen Peroxide

Formaldehyde
Not quantifiable enough to be
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validated

GREEN vs. cGMP

HVAC
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
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Fan VFDs

GREEN vs. cGMP

HVAC
Green
cGMP
BMS time management of BMS time management
airflows becoming more
of airflows done if air
common
classification not
compromised
May Introduce unclean
Enthalpy Wheel
particles into air supply
IAQ Maintained by
CO2Measurements

NA to process areas
(heat load, cleanliness)15

GREEN vs. cGMP

Administrative/Engineerin
g

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 16

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 17
building experience.

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 &
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equipment

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
19

Green vs. cGMP

Disposables (Solids/Liquids)
GREEN(Modifications)
Limited-Unique to each operation

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

Attempt to recycle/reuse (firewater, lawn Off spec distillate

watering)
RO Reject
Attempt to use aqueous or supercritical
Clean Steam Condensate
gas (CO2 is carbon neutral)

CIP Fluids
Solvents (sometimes organic)

Minimize Packaging Materials

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Special packaging needed for cGMP

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_files/Braunegg_Bulk.pdf

21

Green DesignAPI 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 DesignAPI 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 nongreen practice
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Green and cGMP

Design of Buildings
References
Green Building Basics- California Integrated Waste
Management Boardhttp;//www.ciwmb.ca.gov/GREENBUILDING/Basics.htm
Tai-Lee, Oka LEED Certification Primer
http://www.reedconstructiondata.com/articles/read/leedcertification-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_files/Braunegg_Bulk.pdf
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