1. Using the TRI to
Assess Application of Green Chemistry
Practices by the Pharmaceutical Industry in
Achieving Sustainability
Stephen C. DeVito, Ph.D., R.Ph.
U.S. Environmental Protection Agency
Washington, DC
October, 2012
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U.S. Environmental Protection Agency

2. Sustainable Development:
An Ongoing Priority
“Meeting the needs of the present generation
without compromising the ability of future
generations to meet their own needs.”
( From: C.G. Brundtland. “Our Common Future”. The World Commission on
Environmental Development, Oxford Univ. Press, Oxford, 1987.)
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3. National Academy of Sciences
Sept. 2011: Report on EPA and Sustainability
• 4.1. Key Recommendation:
“EPA should develop a
“sustainability toolbox” that
includes a suite of tools for
use in the Sustainability
Assessment and
Management approach.”
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4. Green Chemistry
• That sub-discipline in chemistry that strives to develop
environmentally friendly chemical products through
synthesis pathways that neither use or generate
hazardous chemicals or wastes;
• Evolved in EPA/OPPT’s Industrial Chemistry Branch in
the early 1990s following passage of the Pollution
Prevention Act (PPA) of 1990;
• The practice of Green Chemistry is a primary means of
achieving sustainable development.
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5. Example: Commercial Synthesis of Acetophenone
Time-Honored Synthesis of Acetophenone( a TRI chemical):
3 + 2 CrO3 3 + Cr2(SO4)3
OH + 3 H2SO4 O + 6 H2O
Phenethyl alcohol Acetophenone
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6. Example: Commercial Synthesis of Acetophenone
Time-Honored Synthesis of Acetophenone( a TRI chemical):
3 + 2 CrO3 3 + Cr2(SO4)3
OH + 3 H2SO4 O + 6 H2O
Phenethyl alcohol Acetophenone
This synthesis:
6

7. Example: Commercial Synthesis of Acetophenone
Time-Honored Synthesis of Acetophenone( a TRI chemical):
3 + 2 CrO3 3 + Cr2(SO4)3
OH + 3 H2SO4 O + 6 H2O
Phenethyl alcohol Acetophenone
This synthesis:
- requires the use of two TRI chemicals (one of which is a known
human carcinogen);
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8. Example: Commercial Synthesis of Acetophenone
Time-Honored Synthesis of Acetophenone( a TRI chemical):
3 + 2 CrO3 3 + Cr2(SO4)3
OH + 3 H2SO4 O + 6 H2O
Phenethyl alcohol Acetophenone
This synthesis:
- requires the use of two TRI chemicals (one of which is a known
human carcinogen);
- generates a TRI chemical (also a known human carcinogen) as a
waste and in large quantity;
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9. Example: Commercial Synthesis of Acetophenone
Time-Honored Synthesis of Acetophenone( a TRI chemical):
3 + 2 CrO3 3 + Cr2(SO4)3
OH + 3 H2SO4 O + 6 H2O
Phenethyl alcohol Acetophenone
This synthesis:
- requires the use of two TRI chemicals (one of which is a known
human carcinogen);
- generates a TRI chemical (also a known human carcinogen) as a
waste and in large quantity;
- is only 42 % efficient.
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10. Example: Commercial Synthesis of Acetophenone
Time-Honored Synthesis of Acetophenone( a TRI chemical):
3 + 2 CrO3 3 + Cr2(SO4)3
OH + 3 H2SO4 O + 6 H2O
Phenethyl alcohol Acetophenone
overall synthesis efficiency only 42 %
"Green Chemistry" Synthesis of Acetophenone:
catalyst
+ 0.5 O2 + H2O
OH O
Phenethyl alcohol Acetophenone
overall synthesis efficiency = 87 % !! 10

11. The Practice of Green Chemistry has
Become Widespread in Some Industry Sectors
• Particularly in the pharmaceutical manufacturing sector;
• Examples of drugs made from “green” syntheses:
– Sildenafil citrate (Viagra®)
– Sitagliptin phosphate (Januvia®)
• Merck & Company received EPA’s Presidential Green Chemistry Challenge
Award
– Pregabalin (Lyrica®)
• See the Green Chemistry Institute’s Pharmaceutical
Roundtable website for more information.
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12. The greener synthesis of Viagra® alone uses considerably
less solvent (both in quantity and specific solvent)
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15. Release Reductions are Sector-Wide:
Decline in releases is seen amongst the top ten pharmaceutical
companies as well as the rest of the industry
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16. Preliminary Conclusions & Next Steps
The results of our analyses indicate that the
implementation of green chemistry by the pharmaceutical
industry is reflected in the TRI data.
The results more broadly suggest a potential for the use of
TRI data as a practical tool to track environmental
progress (or lack thereof) within all manufacturing sectors.
We are currently identifying those TRI chemicals for which
the pharmaceutical industry reports fewer quantities.
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17. Acknowledgements
Abt Associates
Dana Lazarus
Cheryl Keenan
Becca Fink
George Washington University (Dept. of Chemistry)
Dr. Adelina Voutchkova-Kostal
Catherine Munro
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