1. Environmental Decision Making & Metrics Session: Methodologies for Assessment and Sustainability Room Location: South American AB Tuesday, June 24, Sharon W. Austin, Green Engineering Program, Office of Pollution Prevention and Toxics
Hello and glad to be here.
CEB provides technical support to many OPPT activities in the areas of chemical engineering, industrial hygiene, occupational exposure and env. releases. We also manage the GE activities.“
In September at the Seize the Moment conference, Dave Constable presented a lot of information on pharma operations and impacts of solvents. This has been incorporated within this presentation and slides were prepared in consultation with David / industry, with blessings.

2. AGENDA Environmental Footprint and Successes Cumulative Waste Loads
Manufacturing Inputs & Outputs (Releases)
Post Treatment Inputs (Releases) and Outputs
Off Site Incineration Metrics
Flow Sheet – Opportunities / Barriers / Metrics
GE Stewardship Initiative – 3 R’s: Reduce, Recover, Reuse
Mission / Project Goals
Manufacturing 3 R’s – Opportunities, Barriers
Post Treatment Metrics – Chemicals, Energy & GHG
Puerto Rico Pilot / Example
AIChE Annual Meeting Topical Conference: Government Programs and Partnership Session

3. Cumulative Waste Loads for a “Typical” Pharmaceutical
For API manufacture:
“Typical” manufacturing yield from a single stage ranges between 35 and 95% with an average of 86%
A “typical” primary manufacturing process is on the order of 6 stages with an overall yield of %
Overall yield does not capture use of reagent, solvent, catalyst. If these are included the average total materials use is 16 kg/kg of stage product (intermediate).
Even with a 100% yield at each stage, a 16 kg/kg materials use would result in an overall Mass Productivity of about 1%.
NO GE activity can replace reductions made by GC solutions in reducing # of stages
99 kg waste to yield 1 kg API - - and this is at 100% yield at every stage. Paradigm shift to look in other places, and have the ability to make these optimizations.
Typical:
86% yield per stage
6 stages
Total materials avg 16 kg / kg product (intermediate or API)
At 100% yield euqated to 99 kg waste to yield 1 kg api
Like . .
The SOLVENTS!! (like, it’s the Economy, __)
99 kg of waste to yield 1 kg of API!!!
Adapted from / Courtesy of: David J. C. Constable, GlaxoSmithKline

4. Pharmaceutical Flow Diagram - Manufacturing Focus Opportunities
Largest Volume of chemical
Variety of Uses
Cumulative through various production stages
Typical focus has been on feedstocks – optimization of the horizontal (GC solutions at reducing stages have greatest impact in reducing solvents generated)
FOCUS on the VERTICAL – SOLVENTS INPUTS and OUTPUTs - --
Specifically on outputs - - those streams (already measured / some TRI reported) of output releases going to post treatment operations
Both On and Off site
Focus on Solvent & Solvent / Water Inputs and Outputs

5. Next .... Off Site Incineration Metrics
Pharmaceutical Flow Diagram – Post-Treatment
Environmental Footprint:
Not manufacture, but Post Treatment unit operations / peripheral support systems
Chemical / Water destructions
BTUs – gas / oil / electricity
GHG
Incineration: off site – no energy recovery, on site – energy recovery
Next Off Site Incineration Metrics

6. 2006 TRI & Post-treatment LCI Models – Off-Site Incineration Metrics
TRI 2006 – NAICS and – pharma sector off site incineration (m) codes
Incineration ONLY model run. (no energy recovery included)
Of the 122 million lbs chemical – thermally destroyed, no longer available for use –
~50 were water soluble (carried 50% water) making aqueous organic mixture with 25% water content
4 million gallons water incinerated – thermally destroyed, no longer available for use
Reguired 90 trillion BTUs to incinerate
Generated 140,000 metric tons, GHG primarily CO2
Top Solvents: Methanol (soluble), dichloromethane (insoluble)
All primary feedstocks
Dow announced 20% price increase 05/29/2008 (Washington Post Express)

7. Where to Focus? What to Measure?
Pharmaceutical Flow Diagram:
Decision Making and Metrics
Where to Focus?
Opportunities:
Barriers: Chemical Liability of feedstocks still in solvents
RCRA
Business Case
How / What to measure:
Baseline: output streams to post treatment
Include chemicals / water (destroyed), energy, GHG in metrics
Add to baseline with three R’s - - environmental clarity – top two solvents
Where to Focus? What to Measure?

8. Green Engineering and Sustainability for Pharmaceutical Processes
Mission: Reduction, Recovery and Reuse of solvents. Solvents as secondary product, not waste.
Project Goals:
Remove barriers, perceived or real, on the reduction, recovery and reuse of these solvents and
Provide the business case in the reduction, recovery and reuse of these solvents in chemicals, energy, emissions, water and other economic and environmental benefits.
Work propelled by activities in Puerto Rico - - elimination of TDS / off site incinerated waste pick up
Needed to start recovering
STOP FOCUSING SOLELY ON THE CHEMISTRY OF REACTANTS
Start with superior replacements – demonstrate comparabilty through MASS (LCA) and ECONOMIC Balance

9. Green Engineering Pharmaceutical Initiative:
Reduce , Reuse, Recover – Decision Making
GE Manufacturing Flow Diagram with the three R’s
Reduce Activities: Input Streams Process Optimizations, RX concentration,
Reuse:
In Process: Ideal sets of solvents
Out of Process: DOC / NIST /MEP By Product Synergies – Third Party Markets
Recovery: New RCRA Law Redefines Solid Waste
Minimize releases to post treatment – measure streams
Metrics based on not only chemicals, but energy, GHG and water saved

10. Green Engineering Pharmaceutical Initiative:
Reduce , Reuse, Recover - Metrics
GE Post treatment diagram – output streams
For BASELINE metrics
Minimize releases to post treatment – measure streams
Metrics based on not only chemicals, but energy, GHG and water saved.
Metrics example just for off site incineration
Did not, but can, incorporate:
Energy Recovery
WWT – large electricity
Solvent Recovery
Add up – based on material flow,
Env Clarity database, works in partnership
LCA for soluble, insoluble solvents
EPA – risk component, property assessment tools (SF), material flow (ChemSTEER)

11. Incineration Treatment Module: Calculation Sheet
Puerto Rico – Energy
OFF siote incineartion model run for PR 2006 reported TRI solvents
First three columns are constant
4th column: Enter KG amounts
Remove row(s), adjust total aqueous equation
Run did not include Energy Recovery

12. Incineration Treatment Module: Calculation Sheet
Puerto Rico - Emissions
GHG emissions from post treatment off site incineration
Energy Recovery not included
Does also not include WWTP, though water emissions calculated
Does not include landfill, though solid waste emissions calculated
'* Based on the models published in: Jimenez-Gonzalez C, Overcash MR and Curzons AD. J. Chem. Technol. Biotechnol. 71: (2001)

13. Green Engineering Pharmaceutical Initiative:
Reduce , Reuse, Recover – Puerto Rico as Pilot
DOC / NIST / MEP
Scorecard.org: other uses
Third party markets
Baseline Metrics: output streatms
Add to case study: application of the three Rs

14. AIChE Annual Meeting - November, 2008 Pharmaceutical Topical Conference
Government programs and partnership sessions:
Reduce: sessions one and two
Reuse: sessions one, three and four
Recover: session 5 – new RCRA law
FDA – Green Product quality

15. So with that and in closing . . .
THANK YOU! 
&
???Questions???
Sharon Austin
(202)
If the FDA could come in and say: If you make these kind of process changes that are not going to effect product quality, we would not get ‘aggitated’, file 483, etc would significantly shift how pharma operates and open door(s) to several opportunities.
Many out in the audience, especially industry, are probably thinking: “All of this is good, but we do not necessarily have the flexibility to just make these changes - - especially if they impact, even positively, on our purity profiles”
New, collaborative term we are introducing: evolved while preparing sessions
Chris will let you know more - -- but I got his specific approval / agreement on this slide before including in this presentation which he was happy to do.