Greener drug design, rather than wastewater treatment, is crucial to combating the pharmaceutical pollution crisis. (Getty Images)
The planet’s ecosystems are being contaminated with active pharmaceutical ingredients (APIs) that are a growing danger to wildlife and human health.
Environmental protection efforts have mainly been focused on upgrading wastewater treatment infrastructure to remove drugs before they are released into waterways effectively.
But greener drugs must be designed to minimise environmental effects, said 17 leading international scientists who published a new study in the journal Nature Sustainability on Wednesday.
“Greener drugs reduce the potential for pollution throughout the entire cycle,” said Gorka Orive, a professor of pharmacy at the University of the Basque Country and one of the study authors.
Humans are living in an increasingly medicated world with pharmaceuticals indispensable in modern healthcare and vital for the future. But humanity’s increasing dependency on pharmaceuticals has come at a major cost, they said.
Discharges to the environment during drug production, use and disposal have seen ecosystems being contaminated with mixtures of APIs, as well as their metabolites, additives, adjuvants, excipients and transformation products.
“A wide variety of drugs have now been detected in environments spanning all continents on Earth,” said Michael Bertram, a researcher at the Swedish University of Agricultural Sciences and one of the authors of the study.
“Exposure to even trace concentrations of these drugs can have severe impacts on the health of wildlife and human populations and have already led to severe population crashes in vultures throughout India and Pakistan, as well as widespread sex-reversal of fish populations exposed to the human contraceptive pill.”
The team said pharmaceutical pollutants represent a particularly complex challenge given that hundreds of different drugs have been detected in ecosystems globally that have a wide range of effects, including anti-anxiety medications, antidepressants, antibiotics and even illicit drugs such as cocaine and methamphetamine.
“Drugs must be designed to not only be effective and safe, but also to have a reduced potential risk to wildlife and human health when present in the environment,” said Orive.
Environmental pollutants
It is the same characteristic of pharmaceuticals that makes them effective in human and animal patients that also renders them particularly hazardous environmental pollutants: drugs are specifically designed to have biological effects at low doses.
The extent of API pollution was shown recently in a large-scale geographical study that measured 61 different drugs in river water taken from 1 052 locations in 104 countries, the study said.
About 43% of the sampled sites had levels of at least one drug that exceeded what is considered safe for ecological health. At the more-contaminated sites, complex mixtures of many APIs were detected, including a range of human and veterinary medications.
Threat to wildlife
For decades, evidence has grown that exposure to trace concentrations of APIs and their mixtures can cause severe developmental, physiological, morphological and behavioural alterations in wildlife.
“For instance, male fish exposed to the contraceptive oestrogen 17α-ethinyloestradiol were feminised and had associated reproductive impairment, which precipitated a severe population collapse in a whole-lake experiment,” the study said.
Any such changes to the survival and reproduction of API-exposed species will inevitably have cascading effects on the ecology and evolution of wildlife populations and communities, potentially driving population declines and local extinctions, it added.
Even unexposed species may be affected because of indirect effects such as reduced prey availability or increased competition.
“API pollution poses a threat to humans and wildlife alike, as seen in the case of antibiotics released into the environment that can act as a selection pressure promoting the mobilisation and horizontal transfer of a wide range of antibiotic resistance genes,” it said.
The problem of API pollution is unfolding against a backdrop of multiple other human-caused pressures on biodiversity and ecosystem services.
These include a changing climate, habitat destruction and fragmentation, over-exploitation of natural resources and invasive species, together with the contamination of ecosystems with other pollutant classes, particularly in rapidly urbanising areas.
“APIs and their breakdown products pose a particular threat to biodiversity given that many have effects at extremely low exposures (for example, parts per billion to parts per trillion) and challenge existing regulatory determinations of chemical persistence, bioaccumulation and toxicity,” the study said.
Consequently, wildlife may not sense API residues and may be unable to actively avoid contaminated habitats.
“Indeed, many aquatic species are attracted to wastewater outflows due to increased nutrient (and, hence, prey) availability and heightened temperatures, resulting in prolonged exposure to diverse cocktails of APIs, their breakdown products and other contaminants.”
Reforming the drug life cycle
To reduce drug pollution, the pharmaceutical industry and its customers need to evaluate and reform many aspects of the complex life cycle of drugs.
“We need more informed and sustainable prescribing practices and usage, given that the most environmentally sustainable pharmaceutical is one that is not required and not prescribed,” the study says.
There will be a need for training for pharmacists, physicians, nurses and veterinarians and prescribing guidelines should be produced that consider the environmental effect of medicines.
“Public awareness campaigns will be vital given that there is currently limited awareness of how prescribed and over-the-counter medicines can negatively affect the environment, through incorrect disposal, for example.”
Key to reforming the drug life cycle is the design of greener pharmaceuticals that are more easily and completely degraded in the environment.
Stronger regulation and increased oversight are also necessary, such as through the polluter pays principle, where the polluter should bear the costs of prevention and control measures.
Conventional treatment plants are not designed to remove APIs so wastewater processes need to be expanded and improved to prevent APIs from entering the environment.
At least 48% of all wastewater globally flows into ecosystems without any treatment, “underscoring the urgent need to increase the geographical extent of wastewater treatment infrastructure”, the study said.
To date, only Switzerland has implemented advanced tertiary treatment of wastewater at the national level.
“Moreover, even advanced wastewater treatment is not capable of removing the majority of APIs and can even result in the formation of incompletely degraded by-products that are more toxic than the parent compounds.”
The advanced treatment of wastewater is expected to remain uncommon globally because of the relatively high price tag, trade-offs associated with energy use and resulting carbon emissions and the lack of regulatory implementation and enforcement.
Molecular design of greener drugs is fundamental. Pharmaceuticals and their additives, adjuvants and excipients should be designed not only to be efficacious and safe, but also to be quickly and fully mineralised to carbon dioxide and water after excretion, for example, by environmental biodegradation.
This approach, known as “benign by design”, is a key aspect of green pharmacy and has been successfully conducted with persistent APIs such as fluoroquinolone antibiotics, the study said.
But barriers exist along the path to designing greener, more sustainable drugs. These include increased economic and time investment into research, development and manufacturing processes. These costs will diminish over time because of technological advancements, increasing experience and expertise and economies of scale.
“Some drug classes may be particularly challenging candidates for green redesign, such as those with especially high environmental persistence, bioaccumulation and/or toxicity attributes of concern.
“However, many pharmaceuticals are already on the market that have not been intentionally designed with environmental sustainability in mind but are nevertheless readily biodegradable in the environment. Adding various molecular elements to drugs can reduce their environmental persistence.”