reducing the carbon footprint of the pharmaceutical industry

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Conference Session C11


Paper #
2226

University of Pittsburgh

Swanson School of Engineering

Twelfth Annual Freshman Conference

April 14,

2012


1


GREEN CHEMISTRY AND GREEN ENGINEERING: REDUCING THE
CARBON FOOTPRINT OF THE PHARMACEUTICAL INDUSTRY


Sydney Biggins

(
sab158@pitt.edu
) an
d Rachel Rajcsok (rer45@pitt.edu
)


Abstract
-

Estimations show that the pharmaceutical sector
of the US gross domestic product has an eight percent input
to the nation’s carbon footprint. This input can be reduced
through the practices of green chemistry and green
engineering. These specialties allo
w the pharmaceutical
industry to reduce their carbon footprint.


Currently, the pharmaceutical industry is not taking
action when it comes to changing their negative impacts on
the environment. The hazardous waste from these industries
triggers a cha
in reaction that leads to potentially harmful
side effects to humans and animals.


Preventative measures enacted by the pharmaceutical
industry would change the amount of waste that is produced.
The removal of certain solvents in chemical processes wo
uld
allow for less hazardous waste. Furthermore, altering the
final product’s degradation process would ensure a safer
product for the consumer.


Because of potential health side effects it is important for
the pharmaceutical industry to utilize the p
ractices and
efficiencies of green chemistry and green engineering to
protect the environment

and move towards sustainability in
the industry
.
Exploring how

to reduce the amount of
hazardous waste through altering chemical processes, as
well as changing t
he way the waste is disposed of, is the
main
focus

of this paper.


Key Words



carbon footprint,
environment,
green
chemistry, green engineering, pharmaceutical industry


M
OTIVATION FOR
C
HANGE

Chemical industries are among the most waste
-
contributing
indus
tries in our nation today. “The pharmaceutical
industry is the least efficient” of the chemical industries
topping out at an “average waste
-
to
-
product ratio of 200
times


[1].
The pharmaceutical industry’s large input to the
nation’s carbon footprint a
ffects human life in multiple
way
s. As shown in Figure 1

[2]
, The Life Cycle of
Pharmaceutical Drugs, the output from pharmaceutical
industries creates a vast network of channels that all lead
back to humans.


First, V
olatile Organic Compounds (VOCs) are released
into the atmosphere, affecting the air we breathe.
Then, t
he
carbon dioxide, or greenhouse gas, emissions from burning
excess waste from solvents in chemical processes takes a
major toll on the ozone layer.

A
pproximately 80
-
90 percent
of a pharmaceutical company’s waste mass is going up the
smokestack as carbon dioxide [1].

The same incineration
process creates ash that piles into landfills and gets into
soils.
Next, a
sh in the soil then leaches into ground
and
surface water, which
contaminates

drinking water supplies.
An alternative pathway leads from the industries to the
hospitals and directly to humans via drugs, where harmful
side effects of the solvents used in processes may deactivate
active ingredien
ts of medications. This pathway leads
directly to animals via drugs, which are consumed by
humans, completing another path from

the

pharmaceutical
industry to human
s
.


As this diagram depicts, the output of the pharmaceutical
industry has a widespread

effect on human health and life
processes. The diagram provides an overview of the
systems that require a safer and healthier change. Altering
the processes the industry utilizes is the key step to initiating
a change in the overall industry. There are
certain guidelines
that the companies can use to lower their carbon footprint;
these processes are called green engineering and green
chemistry.


FIGURE 1

L
IFE
C
YCLE OF
P
HARMACEUTICAL
D
RUGS


Green
Engineering

and Green
Chemistry


Green
engineering

and gre
en
chemistry

are important to the
life cycle of a pharmaceutical process, because they act as
guidelines to improve processes that are
not
environmentally
friendly.


Green engineering “transforms existing practices to
promote sustainable development


[3].
This discipline
upholds nin
e standards, as shown in Table I
, that provide the
basis for conservative technologies that break down complex
systems into simpler, more efficient components. The goals
of green engineering are to design processes that ar
e




Sydney Biggins




Rachel Rajcsok

2

economical, all the while “minimizing the risk to human
health and the environment”

[3]

as well as “minimizing
generation of pollution at the source
” [3].


Protection of
human health, as well as the biosphere, is the motivation
behind green engineers. U
sing this approach as well as
thinking critically will provide a strong foundation for green
chemistry.


TABLE I

T
HE

P
RINCIPLES OF
G
REEN
E
NGINEERING
[3]


Principle

1.

Engineer processes and products holistically, use
systems analysis, and integrate
environmental
impact assessment tools.

2.

Conserve and improve natural ecosystems while
protecting human health and well
-
being.

3.

Use life
-
cycle thinking in all engineering activities.

4.

Ensure that all material and energy inputs and
outputs are as in
herently safe and benign as
possible.

5.

Minimize depletion of natural resources.

6.

Strive to prevent waste.

7.

Develop and apply engineering solutions, while
being cognizant of local geography, aspirations, and
cultures.

8.

Create engineering
solutions beyond current or
dominant technologies; improve, innovate, and
invent (technologies) to achieve sustainability.

9.

Actively engage communities and stakeholders in
development of engineering solutions.


TABLE II

T
HE
P
RINCIPLES OF
G
REEN
C
HEMISTR
Y

[4]


Principle

1.

Prevention

2.

Atom economy

3.

Less hazardous chemical syntheses

4.

Designing safer chemicals

5.

Safer solvents and auxiliaries

6.

Design for energy efficiency

7.

Use of renewable feedstocks

8.

Reduce derivatives

9.

Catalysis

10.

Design for degradation

11.

Real
-
time analysis for pollution prevention

12.

Inherently safer chemistry for accident prevention



Green chemistry principles outline the importance for
safer production and output in chemical industries. The
twelve principles of green chemist
ry summarized in Table II

can
allow pharmaceutical companies to minimize costs,
reduce hazardous materials
, and improve the quality of life
for its consumers. The most important stage of green
chemistry is the phase where designing a new chemical or a
new process occurs. At this stage, the principles
can be

taken into account and the product is evaluated. I
f the
product, when complete,
satisfie
s the goals of both green
chemistry and green engineer, the product has sustainable,
safe, and economically stable features.


L
IFE OF A
P
HARMACEUTICAL PROCES
S

Currently, the majority of chemical processes use harsh
con
ditions that affect pharmaceutical products’ active
ingredients. “High temperatures or volatile, and potentially
toxic, solvents

[5
]
” a
re often characteristics of chemical
syntheses. Extremely high temperatures may be necessary
for drug synthesis to occur, but they are not necessarily
safest for the consumer. Up to fifty percent of a drug’s
active ingredient has the possibility of being

deactivated, and
thus, useless to the consumer. Depending on the type of
solvent used in a process, residues of the solvent may be left
in the product after the process concludes. This may have
adverse effects on the product, making them slightly toxic
to
the consumer.


By changing certain characteristics of the pharmaceutical
process, particularly in the production and disposal aspects,
greener and safer outcomes would emerge. Two particular
examples are given for each case.
Specifically, a
lteri
ng the
isolation process of paclitaxel, as well as changing the way
pharmaceutical waste is disposed of, may be the start of a
greener trend in the pharmaceutical industry.

T
HE
P
RODUCTION
P
ROCESS

The Importance of Paclitaxel


Paclitaxel is the active ingre
dient in the drug Taxol. Taxol is
well
-
known for its use in the treatment of ovarian, breast and
other types of cancers. Taxol’s active ingredient inhibits cell
mitosis, which prevents the spread of cancer. Paclitaxel is
ext
r
acted from the bark of Pacif
ic yew trees. Although
beneficial
, the process of extracting the paclitaxel through
chemical synthesis is very wasteful. The bark of the Pacific
yew tree “contains only 0.0004 percent paclitaxel”
[6
]
. With
this small recovery rate, and the maturity rate

of a yew tree
at 200 years, it is impractical to expect a continual supply of
paclitaxel using a chemical synthesis beginning with simple
materials. The scarcity of the yew tree as a resource creates
increased expenses for companies who wish to continue
use
of chemical or total synthesis. With this realization, the
development towards a greener process took place in the
pharmaceutical industry.


The development of a green chemistry process of
obtaining paclitaxel took two decades to reach. The goal
was to create a paclitaxel molecule synthetically in lab by
beginning with raw starting materials and creating a safe
molecule to use in Taxol chemotherapy treatment. Initially,
a chemical synthesis of forty steps was utilized in order to
reach a usable,
but still scarce at two percent yield, amount




Sydney Biggins




Rachel Rajcsok

3

of the ingredient for the drug Taxol
[6
]
. In total synthesis of
paclitaxel, approximately twelve solvents were used to
create intermediates and obtain a pure sample of paclitaxel.
These solvents included: ace
tone, methanol, toluene, and
ethyl acetate. Although these solvents are used in many
chemical syntheses, they have also been proven to affect the
active ingredients in the final pharmaceutical product by
essentially destroying the molecules
[5
]
.


Af
ter total synthesis was utilized, and the end product
results were more cost expensive than beneficial, an attempt
at a semi
-
synthesis was made. Semi
-
synthesis of paclitaxel
involved fewer steps and began with cheaper raw materials.
The intermediate 10
-
d
eacetylbaccatin III (10
-
DAB) is found
naturally occurring, and thus was used as a starting point on
a pathway of eleven chemical steps and seven isolations
[6
]
.
Although it proved to be the better environmental
alternative, considering it was naturally oc
curring instead of
synthetically developed, it did not eliminate the issue of
using thirteen different solvents and just as many reagents.
In addition to thirteen solvents, the process also includes
about thirteen reagents and catalysts [3]
.

These reagent
s and
catalysts are added to a synthesis in the intermediate stages
in order to manipulate the 10
-
DAB into different molecules
until it reaches the same molecular level as paclitaxel.
Solvents, along with reagents and catalysts, begin to create
many oppor
tunities for the active ingredient paclitaxel to be
influenced or “watered down” essentially.


After many attempts at creating an ideal method of
developing the very useful Taxol drug in a lab, a third
attempt was found to be the most safe and succes
sful. These
previous processes were discarded and plant
-
cell
fermentation was developed with the hopes of high yield and
safer conditions.

Figure 2 compares the steps it takes to
undergo semi
-
synthesis to the steps of plant cell
-
fermentation, in a general

manner.
It also provides the
structure of paclitaxel obtained from cells involved in plant
-
cell fermentation.




FIGURE 2

C
OMPARISON OF SEMI SY
NTHESIS TO PLANT CEL
L FERMENTATION
[7]





Plant
-
Cell Fermentation


The creation of Plant
-
Cell Fermentation Technology is
credited Phy
ton and Bristol Myers Squibb, pharmaceutical
companies
. The process involves non
-
invasive procedures
that do not use traditionally harsh conditions, such as toxic
solvents under high temper
atures.

This fermentation process
allow
s

large
-
scale commercial production of paclitaxel to be
used in the drug Taxol. A fermenter that is capable of
holdin
g approximately 75,000 liters
[8]

is used to assure a
yield of product

that is greater than previo
us methods
. The
specifics of the plant
-
cell fermentation process provide a
clear view into a safe alternative to chemical synthesis.


Plant
-
cell fermentation has four major steps to obtain a
final product: explanting from yew trees, callus formation o
n
an aqueous medium, large
-
scale fermentation, and finally
purification. Although a lengthy process, plant
-
cell
fermentation has proven to be the safest and the most
successful. The first step of plant
-
cell fermentation involves
obtaining a sample of pac
litaxel from a yew plant. An
explant culture is defined as a sample of tissue removed
from a healthy plant. Most often in the case of the yew tree,
for plant
-
cell fermentation, needles from the Chinese yew
are used as the explant culture. From this expl
ant, about one
gram of cells are extracted and used for further steps.


After removing an explant from the yew, the next critical
step is to take the sample and increase growth. This falls
under the first step of fermentation. “When explants are
provi
ded with favorable conditions and suitable media, a
mass of unorganized cells called call
us cultures can be
produced”
[9]
. During this step, the mass of cells extracted
increases in size. As the cells are grown in cultures in a lab,
this eliminates the n
eed for more and more yew trees,
creating a solution to the decrease in population of this tree
type. The explant begins on a plate of solid agar, and next, it
is moved to a p
late of liquid growth medium
[10]
. The cell
sample from the yew tree is given v
itamins, minerals, and an
organic source of carbon
[13]
, which are acceptable
alternatives to using excessive harsh solvents to manipulate
the paclitaxel molecule for high yield.


Allowing cells to grow on a controlled environment
medium creates a la
rge output of viable cells to be used in
the next step of plant
-
cell fermentation. The cells are in a
very conditioned environment that is closely monitored, for
example, the growth mediums must be changed weekly.
Once a substantial amount of callus is f
ormed, the sample is
fermented in a second phase. During this phase, main
production occurs. The cells are continued to be growth
-
controlled under specific conditions, which include being
provided with

a special production medium
[10]
.


The result

of the second fermentation phase is a large
sample of crude Taxol. The large
-
scale product is taken and
purified through chromatography or recrystallization, typical
purification techniques of chemists involved in the syntheses
of drugs. This step is ne
cessary to assure that a pure, active
ingredient drug yield is produced.





Sydney Biggins




Rachel Rajcsok

4


FIGURE 3

P
LANT
C
ELL
F
ERMENTATION
P
ROCESS
B
REAKDOWN
[10]



Figure 3 demonstrates the complex process of plant
-
cell
fermentation, eight steps that may be grouped into four
gener
al steps as presented previously. The production cell
bank that is involved in the first step is the frozen explant
supply. This is used to continue the plant cell fermentation
process to the solid agar growth phase. The so
-
called “seed
build
-
up” is the

cell growth on the liquid medium, which
continually provides the cells with their needs to mass
produce. The fermentation steps are the key components to
this process and are split into two to assure proper yield.
The whole broth extraction portion of t
he process is the
actual removal of crude paclitaxel that has been amassed
throughout the system. Finally, there exist two purification
steps, chromatography and crystallization, before the final
pure sample is able to be distributed as Taxol.


Throug
hout the whole process, approximately five
solvents
are

used


a significant decrease

from previous
methods. Table III

shows in detail approximately how much
solvent was used in the semi
-
synthesis of Taxol versus the
plant
-
cell fermentation of Taxol. Ten

solvents that are used
in semi
-
synthesis of Taxol were entirely eliminated during
the plant
-
cell fermentation process. The amount of total
organic solvent used is higher in plant
-
cell fermentation than
it is for semi
-
synthesis, which is accounted for in
the amount
of the solvent acetonitrile. Acetonitrile, however, may be
recycled for use from the fermentation processes to be
reused for chromatography purification, turning this
abundance into a benefit. Most importantly, the solvent
tetrahydrofuran was
eliminated in plant
-
cell fermentation.
This solvent has explosive qualities that are better left out of
drug synthesis, if given an appropriate alternative.


TABLE III

S
OLVENT
U
SE IN
S
EMI
-
SYNTHESIS
V
S
.

PCF

R
OUTES
[10]



The
Effects
of These Methods


Observing an overall summary of the benefits of plant
-
cell
fermentation provides insight as to why this process proves
to be the most beneficial. Plant cultures naturally occurring
in nature are used as the starting materials, instead of raw
materials. T
his assures consistent outcomes because the
starting materials are naturally the same for each process. A
great reduction in solvents and reagents allows for paclitaxel
remaining more pure
.


A great deal of environmental strain is reduced, as well.
A
pproximately 250 kilograms of Taxol is needed for cancer
treatment in the United States annually. In order to reach this
quota, the bark of 360,000 yew trees must be harvested per
year. Not only is this wasteful, but it is expensive to make
the Taxol, cos
ting about $200,000 to $300,000 per kilogram
[11]
. With plant
-
cell fermentation, there is no need to
continually create biomass from unused yew trees, in order
to obtain high yield of paclitaxel. One to three milligrams of
Taxol per liter is generated in
plant
-
cell fermentation for
every 25 grams of bark used in chemical synthesis
[11]
. The
yew needles provide sufficient amounts of paclitaxel needed
for the starting materials of this method, rather than using
the entire bark of the tree in chemical synthes
is.
[11]

Using

plant
-
cell fermentation, approximately thirty
-
two metric tons
of hazardous waste has been reduced in five years of
production [3]. This amount of reduced hazardous waste
alone should be motivation to move towards greener
methods.


The G
reen Chemistry Resource Exchange evaluates
chemical processes using the principles of green chemistry
.

Based on their evaluation of plant cell fermentation
, four
principles of gre
en chemistry were accomplished.
Those
principles utilized included: less haza
rdous chemical
syntheses, use of safer solvents and auxiliaries, designs for
energy efficiency, and use of renewable feedstocks. Plant
-
cell fermentation
has shown

to be the best alternative for
paclitaxel production, and thus, the principles of green




Sydney Biggins




Rachel Rajcsok

5

chem
istry and green engineering
have led

the way to a safer
chemical process.

T
HE
D
ISPOSAL PROCESS

Defining Pharmaceutical Waste


Before we can try to manage pharmaceutical waste, we have
to define what it actually is. When dealing with
pharmaceutical waste there are two categories that the waste
can be placed into. The first category is nonhazardous waste
and the second is hazardous

waste. “Dealing with the
disposal of waste, the Federal Resource Conservation and
Recovery Act (RCRA) has been in place since 1976”

[1
4
]
.

This act outlines specific methods to dispose of waste and
particular guidelines to define what type of waste needs
disposed.


Nonhazardous waste is considered to be waste that is
opened and unused or partially unused. “Some examples of
this categor
y of waste are unusable medication that has been
spit out or dropped by patients, partially used or empty bags
and tubing that once contained drugs, partially used or
empty bottles and vials. Also medications that are expired
can b
e considered nonhazardous

waste


[1
4
]
.


The second category of waste is hazardous waste. The
Resource Conservation and Recovery Act has outlined
specific categories that hazardous waste can be placed in; it
is a general guideline for defining what waste is hazardous.
“Drugs de
emed hazardous by Federal Environmental
Protection Agency
regulations are categorized as ‘
P list,
’ ‘U
list,’ or ‘
c
hemical (D
-
list)


characteristic


[1
4
]
.

U
-
list drugs
are considered to be any item that is toxic, examples are
phenol and lindane. The P
-
list

drugs are drugs that are
considered acutely toxic, examples are epinephrine and
nicotine. For P
-
listed items, the drug and container are both
considered hazardous.


Drugs placed in the D
-
list category are determined by
four characteristics of the phar
maceuticals: ignitability,
corrosivity, reactivity, and toxicity. Pharmaceuticals that
produce waste with one of these characteristics are placed in
the D
-
list. The definition of ignitability means the drug
contains more than 24% alcohol concentration, for

example
rubbing alcohol. When deciding if the waste is corrosive or
not considering the pH of a product is key. Any waste that
has a pH of 2 or lower, or a pH of 12.5 or higher, is
considered to have corrosive properties and therefore, it is
hazardous. Wh
en dealing with the reactivity category, any
solution that reacts violently with water or releases harmful
gases and vapors when mixed with another chemical is
considered reactive. The last characteristic, toxicity, is
determined by the concentration of a
heavy metal.

For
example, metals such as barium and cadmium are considered
toxic. Once one of these characteristics has been found in the
waste of the pharmaceutical drug it can be placed in the D
-
list.


Making an Alternative Disposal Plan


There is a ne
ed to create some type of alternative disposal
plan for pharmaceutical waste in order to better our
environment, or else the harmful side effects could keep
growing.
“The waste that we defined from pharmaceutical
products has been found in 139 streams samp
led in the 30
states across the country, 80% contained one or more
organic wastewater contaminants. Many of the organic
wastewater contaminants were pharmaceuticals from
common prescriptions and nonprescription products”

[1
4
]
.

Some effects from the waste g
etting into our stream water
and eventually in our sink water (refer back to Figure 1) are
very harmful. Children having neurological disorders, cancer
from hormone defects, and also infertility are a few
examples of the serious harm that waste in our stre
am waters
can create. There are certain steps that can be established to
make the disposal of the drugs a more efficient and
beneficial process.


Landfills are the main disposal site for pharmaceutical
products. When disposing of nonhazardous waste, it

is
acceptable to place the waste in a landfill, but it is not the
safest method. A better approach, for the environment,
would be to place the waste in a medical waste incinerator.
Some nonhazardous waste, however, should be disposed of
as if it were haza
rdous. For example, a chemotherapy
intravenous drip bag that is partially used should be
discarded the same as hazardous waste, since chemotherapy
agents are considered very dangerous. On the other hand,
hazardous waste cannot be disposed of in landfills
; it must
be disposed of by a Resource Conservation and Recovery
Act permitted incinerator. Usually, the two main waste
streams that hospitals and pharmaceutical companies use are
municipal incineration and incineration of chemotherapy
byproducts in medica
l waste incinerators.



Some solutions to revamp the same procedures of
disposal are
:

creating new waste streams, inventory
management, and reverse distribution. The new waste
streams would dispose of the P
-
, U
-
, and D
-
listed waste. The
waste would hav
e to be labeled correctly and distributed to a
federally permitted RCRA incineration firm in order to have
a successful plan. With the creation of new waste streams,

however,

cost may become a major factor. The new
hazardous waste disposal system would cal
l for more waste
management and costly training for employees, adding to a
company’s expenses. To limit this cost factor, introducing an
inventory management staff could help reduce waste as well
as cost. New management would establish a system of
avoiding

unnecessary prescriptions, using the old stock first
to minimize waste and create minimum inventory levels.


Reverse distribution is another disposal process that deals
with recycling pharmaceutical products, in particular pills.

Approximately 17% of

medication prescribed to patients is
not used, and usually disposed of improperly [15]. This may
add to environmental problems. Unused prescriptions can
be returned to the manufacturer for a sum of money. This




Sydney Biggins




Rachel Rajcsok

6

will reduce the amount of unused pharmaceut
icals in
households, which in return, will decrease the amount of
pills being flushed down the toilet into our stream water and
water supplies systems.
All of these new steps can be put
into use, and therefore create new disposal processes for
pharmaceutic
al products that are environmentally friendly,
as well as economically beneficial in the long run.


Consumer Level Disposal Options


Besides altering the drug chemically, there are safer options
of disposal for
individuals

to take action that are often
sup
ported by pharmacies.
For example, c
onsumers may take
part in a safe disposal process by taking part in Medicine
Take Back programs that are provided by groups in the
communities.
The programs

involve turning old
medications to a dedicated recycling plac
e or returning to
drugs to a pharmacy. The Drug Enforcement Administration
also sponsors a National Prescription Drug Take Back Day
to assist communities in discarding medication.


Alternative methods that involve educating the public on
proper, safer

disposal of medication could eliminate this
problem. For example, mixing unwanted medications with
coffee grounds and disposing of the mixture in a plastic bag
with the regular trash helps to contain drugs in a safer
manner. The most common method of di
sposing
prescription drugs today is flushing drugs down the sink or
toilet. Disposing drugs in this manner causes more harm
than good, as it results in prescriptions drugs in the drinking
water supply, as well as leaching into aquatic environments.


Role
Model Companies



The majority of pharmaceutical companies still rely
heavily on traditional processes. However, there are a few
companies that have started to research green chemistry and
green engineering methods. Two leading industries that
have t
aken initiative to changing to a more environmental
approach have been Pfizer and Bristol
-
Myers Squibb.


Pfizer is one of the largest
-
research based pharmaceutical
companies in the industry today. Some of this company’s
major goals include: decreasing w
aste through recycling and
recovery methods, preventing contamination of water and
soil at the industry
-
level, as well as lessening ozone
-
depletion causing pollution [14]. Stages of these goals have
been reached through using green chemistry and green
engi
neering.


Bristol
-
Myers Squibb has set goals that have been met
successfully for the year 2010 and have issued a new goal
set for the year 2015. Goals that were reached on this list
include: 26% reduction in green
-
house gas emissions and a
42% reducti
on in nonhazardous waste disposal [15].
Bristol
Myers Squibb and Phyton
created this plant
-
cell
fermentation method that eliminated, at minimum, six
solvents.


As shown with these companies, green methods have led
to cutting
-
edge research and innovations that will impact
pharmaceutical processes of many companies to come.

T
HE
D
RAWBACKS AND THE
B
ENEFITS

Utilizing green chemistry and green engineering has both

benefits and drawbacks. The major negative of putting this
new process to use is the cost of equipment and adapting to
this new equipment. The cost of testing the performance of
the new equipment was also high. With new equipment
comes training employe
es and the time it takes to train
employees may cost the company more money than is
reasonable.


However
, the benefits of green chemistry and green
engineering may outweigh these drawbacks. The processes
are more efficient, and although expensive in
itially, they will
pay off in the long run. “In the US, $115 billion was spent
in 1992 on w
aste treatment and disposal” [1
6
]. With new
processes and equipment, the amount of waste produced will
be less, resulting in a lower amount of money going into
was
te treatment and disposal.
The U.S. Environmental
Protection Agency estimates that pharmaceutical companies
generated 530 million tons of toxic waste in the year 2005
[1]. The majority of this estimation
, about ninety percent,
is
due to twenty of the mos
t common solvents

the
pharmaceutical industry uses.
Figures estimate that “63,000
pounds per year of related waste and 800,000 gallons per
year of hazardous waste water” [1
7
] will be eliminated under
green chemistry processes, like the examples given.
Al
though a small impact, it is a small step towards lessening
the hazardous
solvent
waste pharmaceutical companies are
disposing.
Without the harsh solvents and toxic waste, the
employees will have a safer work environment, leading to
healthier conditions.

Another result of the removal of
solvents is a lowered cost spent on raw materials.


S
USTAINABILITY OF
G
REEN
P
RACTICES
:

P
LANT
-

C
ELL
F
ERMENTATION AND
D
ISPOSAL


The carbon footprint of the pharmaceutical industry
majorly affects the carbon footprint of

the nation. With the
high demand of pharmaceuticals in today’s economy, the
industry is a target for green chemists and green engineers to
improve the processes of the industry to make them safer.
Reducing the carbon footprint in this industry can begin

through the previously discussed methods, as was the goal of
this paper. The positive effects of these processes were
supported by evidence, but are the processes themselves
sustainable? An analysis of the sustainability of these
methods is the first ste
p towards creating a plan of action to
increase green chemistry and green engineering practices.


Bristol
-
Myers Squibb promotes “product stewardship” at
their company. One of their missions is to practice safe,
green options to assure quality products

for consumers.
Taxol production is a major contributor towards their efforts




Sydney Biggins




Rachel Rajcsok

7

to uphold green chemistry. As previously stated, the yew
tree takes about two hundred years to reach maturity, and
plant
-
cell fermentation removes the need of harvesting yew
tr
ees. Using plant
-
cell fermentation, a consistent supply is
available within a lab [10]. A renewable resource within a
lab creates a sustainable source to continually produce
paclitaxel without endangering a tree species.


Although the process of plant
-
cell fermentation provides
a more efficient and longer
-
lasting supply of raw materials,
the initial phase for the process takes time. “The
construction of a plant for production of biopharmaceuticals
by cell
-
culture fermentation takes about 4
-
6 years” [7
]. The
length of time it takes to create an appropriate laboratory
may inhibit the pharmaceutical industry from changing to
plant
-
cell fermentation. The technological and scientific
demands that go into plant
-
cell fermentation may contradict
the high dem
ands to manufacture drugs quickly for
consumers [7]. The “starting up” cost of initiating plant
-
cell
fermentation may not leave a company with a profit straight
away, as well as the time deficit involved in building an
appropriate facility.


The overa
ll effects of the new waste streams for the
disposal process are beneficial to the environment. The
issue, however, is whether or not they are economically
feasible. For example, reverse distribution may not be
economically positive for the pharmaceutica
l companies,
because of the additional costs of handling the returned
medications. However, a sub
-
section of the company could
be created in order to handle specifically the issue of
returned medications for reverse distribution. Over time, the
process m
ay become organized and beneficial. Another
issue with the disposal options is the topic of consumer
responsibilities. Consumer participation in programs in
unpredictable, and therefore, not a stable means of disposal.


All in all, these processes ha
ve difficult development
phases, but the resulting effects are more beneficial than
traditional processes.

I
NITIATING
A

C
HANGE

The environment is very important in our daily lives. These
steps and processes of improving the pharmaceutical
industries are ju
st another route to eliminating the over
production of waste in our environment.


By observing the research methods behind the production
of paclitaxel through green chemistry principles, many other
chemical processes may be able to cease total synth
esis and
have cleaner processes. As proven above, the benefits of
creating environmentally friendly systems are many. Safer
work environments, as well as unharmed active ingredients
in pharmaceutical products, are two of the most important
results.


For the disposal process, the first step is to identify which
type of waste the drugs give off. By knowing the impact that
the different types of waste have on the environment,
companies can implement plans of action for disposal of the
various types of wa
ste. By following the guidelines that the
RCRA provides this process can be fairly simple. By using
these guidelines, creating waste streams, and providing the
public with waste education, the pharmaceutical footprint
can greatly be reduced.


There are

other industries that may be able to utilize these
processes, but the pharmaceutical industry is a major
contributor to the waste factor. By using this industry as a
role model, maybe other industries will follow and improve
their processes.
Analyzing the

sustainability of these
processes also allows companies to weigh the costs and
benefits of moving towards a safer, eco
-
friendly way of
manufacturing.
Making these few changes, the resulting
environment would be able to handle the waste of the
industries.

R
EFERENCES

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-
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.

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Sydney Biggins




Rachel Rajcsok

8


[1
4
] ASHP Advantage. “Managing Pharmaceutical Waste: A Discussion


Guide for Health
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Available:


www.ashpadvantage.com/docs/PharmaWaste
-
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.

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[Online]. Available:


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.

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[Online].


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.

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[Online]. Available:


http://www.oeconline.org/our
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work/economy/green
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chemistry
-
innovation
-
resource
-
hub/why
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-
of
-
using
-
green
-
chemistry/green
-
chemistry
-
innovation
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chemistry
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innovation
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study
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blou
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inc
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DDITIONAL
R
ESOURCES

Goodman, Jordan, and Vivien Walsh.
The Story of Taxol: Nature and


Politics in the Pursuit of an Anti
-
Cancer Drug
. 1. Cambridge:


Cambridge University Press, 2001. Print.

A
CKNOWLEDGMENTS

We would like to thank Kayla Reddington for her advising
throughout the research process.

Thanks to
Janine Carlock
of the Writing Center as well for her feedback on the paper.
We’d like to acknowledge
Beth Bateman Newborg for her
overall guidance.
Thank

you to t
he chairs of our session,
Ch
r
is Zivkovich

and Kristin Smith
, for their input and
feedback on our paper.