LONDON Too little is being done either to prevent pharmaceutical residues entering the environment or to assess the risks that poses, according to an OECD report.
Most OECD member countries have risk lists and voluntary monitoring for certain pharmaceuticals in surface waters, but the majority of around 2,000 active pharmaceutical ingredients and their metabolites remain unmonitored and without environmental toxicity data.
And while there is a lack of detailed understanding, a growing body of evidence points to the damage that is causing to wildlife, something that is hardly surprising, given pharmaceuticals are meant to have a biological effect.
Active pharmaceutical ingredients are designed to interact with a living system and produce a pharmacological response at low doses. That makes them of environmental concern even at low concentrations. They are often designed to easily pass biological membranes and can interact with targets that occur not only in humans and farmed animals, but across a range of organisms.
As one example, psychiatric drugs such as fluoxetine, have been found to alter fish behavior, making them less risk averse and so more vulnerable to predators.
Active substances in oral contraceptives cause feminization of fish and amphibians, whilst discharge of antibiotics is driving development of drug resistance.
These are worrying examples, but the impact of most other pharmaceuticals on the environment is less well studied. Nor is there any detailed research on what happens when drug molecules are mixed together, or combine with other contaminants, potentially becoming more toxic.
Pharmaceutical residues are detected in wastewater discharges all round the world and the dawning realization of the extent of this form of pollution, coupled with limited understanding of the damage it is causing, has pushed the issue up the political agenda, said Hannah Leckie, author of the report and leader of OECD's work on water quality.
"There is still a lot we don't know about the occurrence of pharmaceuticals in the environment, and we know even less about the concentrations we find in the environment," Leckie said.
Without adequate measures and policies to manage that problem, the amount of residues released to the environment will keep going up and the risk will increase. In Germany, for example, it is forecast that discharge of pharmaceuticals to the environment will increase by 68.5% from 2015 2045 if no restrictions are introduced.
It is estimated 10% of pharmaceutical products pose a potential environmental risk. The scale of that risk will increase as the population ages and more people in developing countries get access to drugs.
Between 30% and 90% of oral pharmaceuticals are excreted as actives and end up in wastewater. Disposing of unused drugs down toilets and sinks adds to that burden, and current wastewater treatments remove only a small proportion of those residues before discharge to the environment.
Meanwhile, veterinary drugs, and in particular antibiotics used in farming, are discharged directly to the environment, adding to pollution levels.
OECD engaged with the pharma industry over the two years spent preparing the report. "There is a lot the industry can do and that some pharmaceutical companies are doing voluntarily," said Leckie.
One example involves companies going beyond the legal requirements when cleaning waste water before it is discharged from manufacturing plants.
There also is a role for the pharma industry to play in the design of green pharmaceuticals that are biodegradable. "We are seeing a slower response here at the moment," Leckie told BioWorld. Governments could do more in that area. "We need incentives to promote development of green drugs," she said.
Currently, there are mixed views about the potential of green pharmaceuticals to reduce the environmental threat. "First of all, we need a good a good definition," Leckie said. There are a number of barriers to the discovery of green alternatives and a number of possible ways to overcome them.
Some may think the term green pharmaceutical is an oxymoron. Pharmaceuticals must be designed to be stable, in order to reach and interact with their targets. That means the desirable chemical design elements for an effective pharmaceutical are contrary to what is desirable in the environment.
However, Leckie pointed to studies showing stability does not exclude biodegradability, and that biodegradability can improve effectiveness and reduce side effects. "I think this is something governments should be paying more attention to," she said.
Another means of nudging the industry into being more eco-friendly is through sustainable procurement. Sweden, for example, recently published a "wise list," which gives the respective green criteria of drugs that have equivalent clinical effect, to guide prescribers.
"We've seen a number of other countries in Europe looking to develop environmental criteria [for use] in drug procurement. It was a pretty much universal ask from all the stakeholders and it would be good to develop [criteria] at an EU level," said Leckie.
Amongst other policy options, the report suggests the development of a standardized methodology for environmental risk assessment, which could then be incorporated into the drug authorization process. More stringent conditions could be attached to putting a high-risk pharmaceutical on the market, such as eco-labeling, prescription only and post approval monitoring.
Similarly, environmental criteria could be written into good manufacturing practices, with companies being required to disclose details of pharmaceutical waste water discharges across their supply chains.
"I'm not talking about new pharmaceuticals not being approved because of environmental risk," Leckie said. "Human health is the priority, but you can impose measures to mitigate those risks."
New pharmaceuticals are required to include an environmental risk assessment in the application for marketing authorization, noted Leckie. The problem is legacy pharmaceuticals. "There needs to be some pretty hard discussions on how to fill that data gap" she said.
Another idea floated by Leckie is that of extended producer responsibility, a strategy by which all the environmental costs associated with a product throughout its life cycle are added to the market price of the product.
That could perhaps cover the costs of schemes to collect and destroy unused drugs, or to cover the cost of upgrading water treatment plants. Germany currently is exploring the potential for such a scheme, and Leckie said OECD will investigate the possibility in more detail over the next 18 months, as it continues its work on the environmental harm caused by pharmaceutical residues.