Regulating the Environmental Impact of Pharmaceuticals

Pressure is mounting on European legislators to introduce tighter regulations at both the European Union (EU) and national levels on the potentially harmful impact of pharmaceuticals on the environment. Politicians, environmentalists and even medicines regulators are calling for action in the face of increasing evidence that pharmaceutical chemicals used through the whole lifecycle of medicines from production through to disposal are posing a bigger than previously anticipated threat to the environment.

There are, however, divided opinions on what needs to be done. Some groups want stricter regulation of production processes, more consideration of environmental issues when market authorisations are granted and more rigorous rules on disposal of pharmaceuticals. Some regulators, environmentalists and fine-chemical producers support suggestions that tougher environmental standards should be applied to imported APIs. This increase in standards could be done by extending rules on GMPs to environmental protection. Others, particularly most parts of the pharmaceutical industry, believe that voluntary initiatives should be sufficient to eliminate the dangers of medicines in the environment.

The European Federation of Pharmaceutical Industries and Associations (EFPIA), representing research-based companies, concedes that the public wants more information about the risks from concentrations of certain medicines in the environment. “We believe that voluntary initiatives might be a relatively fast and flexible way (of dealing with this issue),” says an EFPIA spokesperson.

European countries concerned
The European Commission appears to be taking its time on the issue. The Commission is expected to release shortly a study it has funded on the environmental risks of pharmaceuticals after its publication was postponed last year (1). In 2015, the Commission is scheduled to issue a strategy document outlining ideas for new regulatory measures after which it will have the option to draw up a draft legislation.

Some countries may not wait for specific proposals by the European Commission. Instead they could enact their own regulatory schemes. This effort could happen among groups of states. Countries bordering the Rhine have, for example, already put forward ideas for international regulations to protect the river from pollutants such as pharmaceuticals.

The countries most concerned about pharmaceutical environmental threats are the Scandinavian states, Germany and its German-speaking neighbours. Sweden has been particularly active in lobbying other EU states for new EU regulations to ensure all risks associated with environmentally harmful chemicals are controlled at their source. “This should also, as far as possible, be a principle underpinning the management of environmentally harmful chemicals in medicinal products for human use,” claimed the Swedish Environment Ministry in a policy communication last year.

The Swedish government has also been taking a global perspective on environmental standards in the pharmaceuticals sector. It first proposed several years ago that the EU should move to extend the scope of GMPs to cover environmental protection in the production outside Europe of both finished medicines and APIs.

Environmental research
A lot of the latest research in Europe on the dangers of some pharmaceuticals, including APIs, to the environment has been done in Germany. With the encouragement of Germany’s Environment Ministry (BUMB), the country’s environment agency (UBA) has been conducting or funding studies in areas such as the contamination by pharmaceuticals of soil and sludge through emissions from production processes, sewage and waste-water treatment plants.

In research funded jointly by the UBA and BUMB, IWW Water Centre at Duisberg-Essen University found in an extensive literature investigation a total of 123,761 incidents of measured environmental concentrations (MECs) of pharmaceuticals across the world, according to the results of the study revealed at a workshop in Geneva in April (2). The majority of these were in concentrations in sewage, waste-water treatment effluent and surface water. Only a small minority were found in soil, sediment and slurry.

Altogether, 559 different pharmaceuticals or their derivatives such as metabolites were found in waste-water treatment influent, effluent and sludge, according to IWW. Another 38 different pharmaceuticals were found in surface, ground and drinking waters. The greatest concentration tended to be in Europe and North America. Among the 16 pharmaceuticals most frequently detected in surface, ground and drinking waters, the majority were in Europe, headed by the analgesic diclofenac and the anti-epileptic carbamazepine. With diclofenac, for example, 36 of the 50 detections were in Europe, most of which were in Western Europe.

“Urban waste water discharge is the dominant emission pathway, while discharge from manufacturing, animal husbandry and aquaculture are important regionally,” Tim aus der Beek, a senior IWW researcher told the Geneva meeting on pharmaceuticals in the environment, jointly organised by UBA and the United Nations Environment Programme (UNEP). He indicated that the problem of pharmaceutical pollution might be even more extensive because of the limitations of instrumental analytics. “The methods available are only [applicable to] some of the thousands of pharmaceuticals manufactured,” he said.

Legislation of environmental impacts
The need to deal with the hazardous effects of pharmaceuticals is highlighted in last year’s EU priority substances directive (3). The preamble to the legislation states, “the contamination of water and soil with pharmaceutical residues is an emerging environmental concern.”

The directive stipulates that after conducting a study on the environmental risks of medicines and drawing up a strategy on how to deal with water pollution by pharmaceuticals, the Commission shall by September 2017 propose measures on their possible environmental impact. These measures, however, would be applied only “where appropriate” and could, therefore, be introduced only at the national level.

Some experts reckon that the phraseology in the directive is so vague that the Commission could avoid taking legislative steps. “A sharper formulation of the text would have been preferable,” Ake Wennmalm of the Swedish-based consultancy SustainPharma told Pharmaceutical Technology.

“On the other hand, so many international initiatives on how to manage pharmaceutical pollution to the environment have been taken recently that DG SANCO (the Commission’s directorate responsible for health and consumer protection) sooner or later has to wake up and realise that they have been overhauled by the reality.”

If the Commission fails to act, there is a danger that certain member states will do it alone. The Swedish government, for example, has set itself targets for a non-toxic environment by 2020. “Concentrations of non-naturally occurring substances will be close to zero and their impacts on human health and on ecosystems will be negligible,” Jerker Forssel, deputy director of the chemicals division of Sweden’s environment ministry, told the Geneva meeting (4). For the moment, however, Sweden is hoping that regulatory initiatives will be taken at the EU, particularly so that risks can, as much as possible, be tackled at source.

“Environmental risks should be factored into the assessment of the benefits and risks of medicinal products,” Forssel said. “There should be a regulatory instrument at the EU level setting minimum requirements for production conditions for the authorised sales of products on the EU market.” The European Medicines Agency (EMA), as well as national agencies, should have environmental databases on substances. “The pharmaceutical authorities should be in a better position to make a first scientific estimation of risks, particularly with regard to degradability, bioaccumulation and long-term environmental effects,” Forssel said.

EFPIA has put forward a broad scheme for environmental protection including greater controls on manufacturing effluents across the industry and an expansion of the system of environmental risk assessment (ERA) applied to new medicines when they are considered for authorisation. ERAs would be extended to the whole lifecycle of a product and to long-established medicines that had not been subject to any environmental assessment, according to EFPIA.

The Innovative Medicines Initiative (IMI), a public-private scheme jointly funded by the EU and EFPIA, has just embarked on a four-year Ecorisk Prediction (ERP) project on the development of ecotoxicological risk assessments based on knowledge from modes of action derived from preclinical and clinical studies. This project will be used in particular for predictions of possible hazardous properties of APIs.

“ERP will provide a validated model to support the evaluation of the ecotoxicological hazards of APIs during the early development process,” Bengt Mattson, co-chair of EFPIA’s task force on pharmaceuticals in the environment, told the Geneva workshop (5).

Nonetheless EFPIA has concerns about environmental standards being enforced through GMP changes. “Such an initiative might divert the focus from product quality and patient safety,” says the association’s spokesperson. “We believe there are other ways, potentially better suited, to reach the same objective of protecting the environment from possible manufacturing impacts.” R&D could be directed, for example, at the development of alternative products with reduced environmental impacts.

For the industry, a major demand is that if any new environmental legislative measures are considered by the authorities to be necessary, they should be additions to existing pharmaceutical regulations. The industry does not want the responsibilities of the environmental standards of pharmaceuticals to be in the hands of agencies that do not understand how to balance the risks and benefits of medicines.

References
1. Ministry of Environment Sweden, Milestone target of increased environmental consideration in EU pharmaceutical legislation and internationally (Stockholm, 31 October 2013).
2. T. aud der Beek, F.A. Weber, A. Bergmann, “Results of Global Database of Measured Environmental Concentrations (MEC),” presentation at Pharmaceuticals in the Environment Workshop (Geneva, 8-9 April 2014).
3. European Union Directive 2008/105/EC, Priority Substances Directive (also known as Directive on Environmental Quality Standards) (Brussels, December 2008).
4. J. Forssel, “Milestone target of increased environmental consideration in EU pharmaceutical legislation and internationally,” presentation at Pharmaceuticals in the Environment Workshop (Geneva, 8-9 April 2014).
5. B. Mattson, “Pharmaceuticals in the Environment (PIE),” presentation at Pharmaceuticals in the Environment Workshop (Geneva, 8-9 April 2014).

About the Author
Sean Milmo is a freelance writer based in Essex, UK, seanmilmo@btconnect.com.