2. Active pharmaceutical ingredients represent a group of
emerging environmental contamination.
It is estimated that worldwide consumption of active
compounds amounts to some 100 000 tons or more per
year.
Even in trace amounts, they are of great concern due to their
continuous introduction into the environment, their impact on
ecosystem and human and veterinary health is of great
importance
3. Our home — Earth — is in danger. What is at risk of
being destroyed is not the planet itself, but the
conditions that have made it hospitable for human
beings.
New York Times, July 1 2007
by Al Gore
5. EPV
The science and activities associated with the detection,
evaluation understanding and prevention of adverse effects
of pharmaceuticals in the environment
Term first coined by Velo
Compared to the west EPV in India is in infancy
6. AIM
To monitor the adverse effects of pharmaceuticals in the
humans through non therapeutic environmental exposure
To ensure that significant issues associated with
pharmaceutical in environment are identified and managed
properly.
7. Pharmacology and Eco-Pharmacology
diffuse i.e. emissions of
medical care units and the
community
aimed, on demand,
controlled
administration
various types of
organisms of different
trophic levels
one type of organismaffected organisms
wanted effects in humans
are often most important
side effects in the
environment
wanted effects, side
effects
wanted effects/
side effects
readily (bio) degradablestabledesirable physico-chemical
properties
an unknown cocktail of
different compounds
one or only a few
compounds at the same
time
number of compounds
administered
Eco-pharmacology
(environment)
Pharmacology
(humans)
8. SOURCES
Patient excretion of the drug or its metabolites via the sewage system.
Direct release from waste water system from manufacturing units.
Hospital or self disposal of unused, unwanted, expired drugs via trash
or flushing.
Terrestial deposition
Sludge application to land,
Leaching from solid waste landfills
Irrigation with treated or untreated waste water
9.
10. Spread of drugs in the environment
The largest flow of drugs into the environment comes from people who
are under medical treatment.
Drugs are eliminated from the body either in unchanged form or as
metabolites in faeces and urine and find their way to sewage treatment
plants (STP).
11. Spread of drugs in the
aqueous phase
Drugs that break down rapidly will be found close to their sources
and only if they have been released in large amounts.
Example - Acetylsalicylic acid
Drugs that are both water-soluble and stable will pass through a
treatment plant more or less unchanged and be dispersed in the
surrounding watercourse.
Example - Bezafibrate and other lipid-lowering drugs
Drugs that are fat-soluble and stable will adsorb to a considerable
extent to sludge particles through the sewage treatment process.
Example - Fluoroquinolones
12. Spread of drugs in the
drinking water
The first pharmaceutical substance detected in drinking water was
clofibric acid , found by a german research group in berlin ten years
ago (stan, 1994).
Since then several drugs (such as bezafibrate, carbamazepine) have
been found in drinking water in germany (ternes, 2001).
13. The city's sewers each day soaks up its citizens' routines, taking in a steady
stream of products. Toothpaste and shampoo may be harmless enough, but
the waste also collects a wide array of medicines people take. Most drugs are
poorly absorbed and metabolized by the body, so it is not unusual that the
majority of a drug would end up intact in the urine. Because all water goes
through toilets at some point, these artificial compounds, some quite
difficult to break down, can eventually find their way into the city's water
supply—even bottled water.
Nature Medicine 12, 376 - 377
(2006)
Drugs down the drain
14. EFFECTS ON LONG TERM EXPOSURE
Chronic toxicity
Microbial resistance
Disruption of microbial ecosystem
Endocrine disruption
Cytotoxicity
Mutagenicity
Teratogenicity
Growth inhibition
15. EXAMPLE - 1
In south-east Asia vultures ingested carcasses of live stock that
has been treated with high doses of diclofenac.
It is estimated that between 10 to 40 million vultures has been
poisoned
Three species of gyps vultures are now critically endangered
due to gout & acute and chronic renal failure.
Government of India has banned diclofenac for veterinary use
16. EXAMPLE - 2
Ethinylestradiol has shown to affect the sexual
development of male fish in extremely low concentration in
the laboratory
Field survey have shown that intersex fish are wide spread
in British river
17. EXAMPLE - 3
Sterility of frogs due to traces of oral contraceptives
pills in water became the cause of decrease in
number of frogs
18. Environmental risk Assessment(ERA)
Now a regulatory requirement prior to launch of any new drug
Assess the environmental fate and effects produce by
pharmaceuticals
Several challenges that has to met if EPV is to effective in
practice like Environment risk management plan
19. Environment Risk Management plans (ERMPs) by EU as a
centralized resource to assess and manage the environment
risk of a drug throughout its life cycle which include
information such as
Physicochemistry
Human metabolism pharmacokinetics,
Preclinical toxicology
Environmental data of the drug
20. EVALUATION OF EPV
PEC : PNEC RATIO
PEC - predicted environmental concentration
PNEC - the predicted no effect concentration.
Ratio (PEC:PNEC) - estimate the maximum concentration anticipated
to occur in the environment
PENC is derived from ecotoxicological test normally in algae, fish.
21. If PEC :PNEC < 1, no further information is required
If > 1 then additional testing required and appropriate risk
management is needed
According to European guidelines, PEC of pharmaceutical
products in water > 0.01 μg.L−1 before further environmental
risk assessment is necessary
22. APPROACHES
Green drug design
Green chemistry in process development
Development of biodegradable product
Minimization of manufacturing emission
Education on rational use of drugs
Improved prescribing practice
Management of unused drug
23. Short term approach:
effluent treatment
Advanced effluent treatment is still the approach that is favoured
despite its increasingly visible technical and economical limitations and
unsatisfactory performance .
This approach is probably not sustainable .
26. Green Chemistry ?
• Green chemistry is the design of
chemical products and processes that
reduce or eliminate the use and
generation of hazardous substances
Green Pharmacy aims at zero pharmaceutical waste in
our environment
27. Daughton proposed the need for “green
pharmacy,” where the life cycle of pharmaceuticals,
from “cradle-to-grave,” including synthesis from
raw materials, production of products, transportation,
storage, deliveries, usage, and disposal, are
appropriately assessed, anticipated, and managed.
28. The most simple and direct way to apply green chemistry in pharmaceuticals
is to utilize eco-friendly, non-hazardous, reproducible and efficient
solvents and catalysts in synthesis of drug molecules, drug intermediates
and in researches involving synthetic chemistry
29. New compounds are effective, efficient, and
readily degradable in the environment
Long Term Risk Management:
Green Pharmacy
identification structures essential for
• efficacy
• (bio)degradability
30. Modification of Structure
Changes Properties
OH
Benzene:
not biodegradable
cancergenic,
not bactericidal
Phenol:
readily biodgradable
not cancerogenic
bactericidal
31.
32. KEY RECOMMENDATION ON EPV
IMPLEMENTATION
BUILDING PERFECT LAWS & REGULATION SYSTEM
DEFINING THE EVALUATION INDEX
CONTINUING THE CLINICAL RATIONAL MEDICATION
TAKE BACK POLICY
POPULARIZING THE CONCEPT OF EPV
STRENGTHENING THE POLICY GUIDED & SCIENTIFIC
RESEARCH OF EPV IN PHARMA FIRMS & ACADEMIA
