Pharmaceuticals in the Environment: The Problem in Perspective

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Pharmaceutical Products in the Environment: Is there a problem?
The “Problem” in Perspective
David Taylor - wca environment
& Thomas Senac - Sanofi

PHARMAS Conference – Nimes June 2013
 Advances in analytical science enable us to see residues of
pharmaceuticals in the environment that used to be invisible.
 These residues are widespread in the environment (mainly in water)
 Most are <1 µg l-1, many are <0.1 µg l-1, Drinking Water <0.01 µg l-1
 The principle source of most pharmaceuticals to the environment
is from the excretion products of patients.
 90% of medicines are estimated to be used by patients as prescribed
 At the levels currently present in the environment:
 Risks to human health are considered to be very unlikely
 Acute effects on aquatic life are considered to be insignificant
 Data on the potential long term impacts is increasing,
and varied, however some significant impacts on
some aquatic life forms cannot be ruled out.
What do we know about PIE?

Pharmaceuticals
Plasticisers
Pesticides Biocides
Flame Retardants
Fragrances
Personal Care Products
Detergents
Pharmaceuticals
But do we have tunnel vision?

What defines a pharmaceutical?
Pharmaceuticals cannot
be defined by any of
their chemical, physical,
structural or biological
properties

Pharmaceuticals cannot be defined by structure
Propofol Insulin
Atorvastatin
Nitroglycerine

It is only the use to which it is put that
defines a chemical as a pharmaceutical.
Warfarin
Any substance has the potential to be used as a pharmaceutical
All substances will exert harmful effects at some concentration
Dimethyl Fumarate
Tecfidera

So what is it that
makes pharmaceuticals
‘different’?

“They are designed to
be biologically active”
 Which also implies that more ‘environmentally friendly’
alternatives could be developed.
 However, few if any drugs are really ‘designed’.
 Our knowledge is simply insufficient to do this
 If design was possible, drug pipelines would be more robust.
 Drugs are ‘discovered’ & then optimised for efficacy & safety.
 This is the fundamental reason why the ‘green by design’
concept cannot currently be well defined for pharmaceuticals
 Even if drugs were 90% degradable they would still be
detectable in the environment (1.0 µg l-1 becomes 0.1 µg l-1)

“They are designed to
be biologically active”
 The implication being that they are therefore of much
more concern than other substances.
 Biological activity shouldn’t be confused with toxicity.
 Only antibiotics and antineoplastics are deliberately toxic
 Mammalian toxicity and bioaccumulation are very, very
unhelpful properties of any potential pharmaceutical.
 Compounds that are toxic to mammals or bioaccumulate will
usually be screened out during preclinical development
Any substance has the potential to be used as a pharmaceutical
All substances will exert harmful effects at some concentration

Pharmaceuticals
are “down the drain”
chemicals
Therefore entry to the environment is
continuous from multiple point sources
BUT This is a common attribute that they
share with many other substances

“Pharmaceuticals could
be a problem because
they might:”
 be metabolised by the body before release.
 breakdown into potentially more toxic substances
 not be fully removed in waste water treatment
 form transformation products during water disinfection.
 disrupt the endocrine system
 interact with each other to increase potency
 interact with other substances to increase potency
BUT These concerns apply to micropollutants in general

“There are only a few Pharma
companies so control is easy”
Research Companies
Generic Companies

Pharmaceuticals are data rich
substances and are getting richer
More information is available on the toxicology of
pharmaceuticals than all other substances put together
Data on toxicology (including mutagenicity, carcinogenicity,
cytotoxicity, histopathology, teratogenicity …), kinetics,
metabolism, mode of action… for humans AND animals.

The risk benefit balance is different
for pharmaceuticals
 Society will usually tolerate a higher level of risk to gain significant
patient benefit.
 Risk benefit assessment of pharmaceuticals is complex.
 Not all side effects are known when the product is approved.
 Trade offs will need to be made between + ve and – ve aspects.
 A balance will be needed between benefit and uncertainties.
 A single regulator is needed to simultaneously weigh ALL the evidence.
 Pharmacovigilance is used to update the assessment
 Pharmaceuticals receive a comprehensive in depth risk benefit
evaluation before they receive a marketing authorisation.
 It is inappropriate to introduce new regulations that override this
carefully balanced holistic judgement.

So why are pharmaceuticals
being treated differently to
other micropollutants?
 Pharmaceuticals can only be differentiated from other substances
as a consequence of their use.
 Compared to other micropollutants pharmaceuticals are:
 Neither more widely distributed nor found at higher concentrations
 Not necessarily more biologically active.
 Likely to be less toxic and accumulative in mammals
 Data rich & likely to have a much higher value to society
 There is thus no reason to treat the pharmaceutical group
differently to other groups of micropollutants
 However individual pharmaceuticals, like any other micropollutant,
might be of environmental significance

DICLOFENAC

Consequences & Actions
Beware the Policy Syllogism
“Something must be done!,
This is something,
Therefore we must do this”
Actions need to address actual
problems and be proportionate

Wrong diagnosis can lead to wrong action

TREATED SEWAGE DISCOVERED
IN OUR DRINKING WATER
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THE DAILY NEWS
www.dailynews.com THE WORLD’S FAVOURITE NEWSPAPER - Since 1879

Monitoring Pharmaceuticals
How to expend large resources to learn nothing of significance.
 The literature is overflowing with data on measurements of the
same few pharmaceuticals in various water bodies.
 This uses very substantial and sophisticated laboratory resources
 We already know that all waters will contain pharmaceuticals
 But academics, regulators & industrialists are already using validated
precautionary risk assessment methods to predict exposures and assess
the environmental and human impact of pharmaceuticals in both their
manufacturing and use
 Meanwhile little or no data exists either for the
concentration of, or the human or environmental impact
of, thousands of other micropollutants.

Any additional treatment technology should be
aimed at the global reduction of ALL those
micropollutants which indicate significant
environmental risk, not just pharmaceuticals
Removal of pharmaceuticals from wastewater
An expensive way to solve the wrong problem

Going beyond compliance
 Working proactively via Trade Associations, Research
Groups & individual companies industry is co-operating
with Authorities, Academics and other stakeholders.
 Continually improving product risk assessments
 Developing intelligent testing strategies
 Improving fate modelling and testing (e.g. PhATE)
 Addressing effluents from manufacturing
 Improving risk assessments, process design & treatment technologies
 Sharing expertise with contract manufacturers
 Promoting unused medicine take back programmes

Conclusions
 Pharmaceuticals as a group are no more of a problem than
any other micropollutant ‘group’.
 Individual pharmaceuticals may pose specific problems but
these should be dealt with on a case by case basis.
 Antibiotics may be a special case
 A satisfactory ERA is needed for all micropollutants
including existing pharmaceuticals.
 A proportionate ‘no-regrets’ approach should apply to
reducing inputs of all micropollutants including
pharmaceuticals to the environment .
 Faulty diagnosis can lead to inappropriate solutions and
wasted resources yet provide no improvement to more
significant problems

Contacts for further information
www.wca-environment.com
solutions@wca-environment.com
Questions?

Supplementary Slides

With a big enough sample analysts can
now find anything, anywhere if they look
hard enough
Decade Detection Limit Ratio Description
1900s 0.1% 1 in 103
Parts per thousand
1930s 1 milligramme / litre 1 in 106
Parts per million
1960s 1 microgramme / litre 1 in 109
Parts per billion
1980s 1 nanogramme / litre 1 in 1012
Parts per trillion
1990s 1 picogramme / litre 1 in 1015
Parts per quadrillion
2010s 1 femtogramme / litre 1 in 1018
Parts per quintillion
???? 100 molecules / litre 1 in 1021
???? 1 molecule / litre 1 in 1023

Pharmaceuticals in Drinking Water
Risk to HumanConsumers in Perspective

PHARMAS Conference – Nimes June 2013 Slide 28University of York - June 2011
Pharmaceuticals in Water – Environmental Impact
Ratio of MECs to lowest reported effect concentrations (Boxall et.al. 2008)

Pharmaceuticals in the Environment: The Problem in Perspective

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