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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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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National Academy of Sciences

• 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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Sept. 2011: Report on EPA and Sustainability

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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Example: Commercial Synthesis of Acetophenone

5

OH

3 + 2 CrO3

+ 3 H2SO4 O

3 + Cr2(SO4)3+ 6 H2O

Acetophenone

Time-Honored Synthesis of Acetophenone( a TRI chemical):

Phenethyl alcohol

Example: Commercial Synthesis of Acetophenone

6

OH

3 + 2 CrO3

+ 3 H2SO4 O

3 + Cr2(SO4)3+ 6 H2O

Acetophenone

Time-Honored Synthesis of Acetophenone( a TRI chemical):

Phenethyl alcohol

This synthesis:

Example: Commercial Synthesis of Acetophenone

7

OH

3 + 2 CrO3

+ 3 H2SO4 O

3 + Cr2(SO4)3+ 6 H2O

Acetophenone

Time-Honored Synthesis of Acetophenone( a TRI chemical):

Phenethyl alcohol

This synthesis: - requires the use of two TRI chemicals (one of which is a known human carcinogen);

Example: Commercial Synthesis of Acetophenone

8

OH

3 + 2 CrO3

+ 3 H2SO4 O

3 + Cr2(SO4)3+ 6 H2O

Acetophenone

Time-Honored Synthesis of Acetophenone( a TRI chemical):

Phenethyl alcohol

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;

Example: Commercial Synthesis of Acetophenone

9

OH

3 + 2 CrO3

+ 3 H2SO4 O

3 + Cr2(SO4)3+ 6 H2O

Acetophenone

Time-Honored Synthesis of Acetophenone( a TRI chemical):

Phenethyl alcohol

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.

Example: Commercial Synthesis of Acetophenone

10

OH

3 + 2 CrO3

+ 3 H2SO4 O

3 + Cr2(SO4)3+ 6 H2O

Acetophenone

overall synthesis efficiency only 42 %

Time-Honored Synthesis of Acetophenone( a TRI chemical):

"Green Chemistry" Synthesis of Acetophenone:

OH

+ 0.5 O2

O

+

Acetophenone

catalystH2O

Phenethyl alcohol

Phenethyl alcohol

overall synthesis efficiency = 87 % !!

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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12U.S. Environmental Protection Agency

The greener synthesis of Viagra® alone uses considerably less solvent (both in quantity and specific solvent)

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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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Preliminary Conclusions & Next Steps

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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.

Acknowledgements

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Abt AssociatesDana Lazarus Cheryl KeenanBecca Fink

George Washington University (Dept. of Chemistry)Dr. Adelina Voutchkova-KostalCatherine Munro