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. 

5. 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

6. 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 GREEN vs. cGMPGovernment Regulation * Leed Certification Primer http://www.reedconstructiondata.com/articles/read/leed-certification_primer/

7. 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) GREEN vs. cGMPArchitectural Features

8. 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 GREEN vs. cGMPArchitectural Features cont’d

9. 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 cGMP NA- most functional rooms not on perimeter Same Generally in offices/support areas not research/production Qualified save even more? GREEN vs. cGMPEnergy Conservation

10. 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

11. 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 GREEN vs. cGMPPlumbing Considerations

12. 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 GREEN vs. cGMPAqueous Based Utilities

13. 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 GREEN vs. cGMPMicroorganisms/Living Things

14. Green Minimal Air Changes/hr Large % recycle Green applications in laboratories Fan VFD’s 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 VFD’s GREEN vs. cGMPHVAC

15. 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) GREEN vs. cGMPHVAC

16. 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 & 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 GREEN vs. cGMPAdministrative/Engineering

17. 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.

18. Green vs. cGMP Common to Both • Successful design/operation (cont’d) • 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

19. 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 Green vs. cGMP High Energy Operations

20. 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 Green vs. cGMP Disposables (Solids/Liquids)

21. 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

22. 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)

23. 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

24. 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

25. Green and cGMP Design of Buildings References • Green Building Basics- California Integrated Waste Management Board- http;//www.ciwmb.ca.gov/GREENBUILDING/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_files/Braunegg_Bulk.pdf