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Various groups and stakeholders from pharma, healthcare, and government are responding to a new draft environmental risk assessment guidance from EMA.
Editor's Note: This article was published in Pharmaceutical Technology Europe's February 2019 print issue.
Pharmaceutical companies, groups representing health professionals and care providers, non-governmental organizations (NGOs), and other stakeholders are currently working on their responses to a draft revised guideline by the European Medicines Agency on environmental risk assessment (ERA) for new marketing authorizations of medicines (1).
The guideline-which will apply to medicinal products authorized at both the centralized and decentralized, mainly national, levels within the European Union-will replace an existing ERA guideline issued in 2006 (2). In fact, this guideline, the first of its kind in the EU, was first drafted almost 20 years ago.
Now, the new guidance is being introduced at a time of growing demands, especially among some politicians and NGOs, for much tighter controls on the environmental effects of medicines throughout their entire lifecycles. As a result, the contents of the document, which is currently going through a seven-month consultation process, could turn out to be controversial for groups wanting environmental risks of pharmaceuticals to be much more strictly regulated.
The 48-page new guideline is much more detailed than the current 12-page version. This is mainly because over the past 12 years the environmental assessment of chemical substances and compounds has become much more sophisticated and complex. As a result, any revised guidance requires a lot more information on how to conduct up-to-date safety profile tests.
EMA’s guideline gives much more prominence, for example, to endocrine active substances (EAS) in the wake of rising concerns about their dangers to the environment, even in small quantities (1).
Much of its advice on testing methods comes from guidance laid down by the Helsinki-based European Chemicals Agency (ECHA), which is responsible for administering the Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH), the EU’s chemicals safety regulation. REACH came into force after the existing ERA guideline in June 2007, since then ECHA has issued a mass of guidelines on the testing of substances.
Another major source for EMA on assessment technologies and systems has been the Paris-based Organization for Economic Co-operation and Development (OECD), a leading provider of international protocols which has been issuing an increasing amount of information on safety test methods.
The likelihood that the new guideline will generate more detailed information on the environmental impact of medicines will be welcomed by environmental scientists and officials in the industry. This is particularly true among those involved in efforts in the pharmaceutical sector to build up large amounts of data on the behaviour of medicines in the environment so that industry can draw up internationally recognized standards of good practice in environmental management, especially in the control of effluent from pharmaceutical manufacturing plants (3).
“Important data will be generated about the environmental effects of new medicines mostly when they are excreted by patients during treatment but which can then be used by industry when dealing with effluent from manufacturing facilities,” Bengt Mattson, co-chair of the European industry’s Inter-Association Task Force on pharmaceuticals in the environment, told Pharmaceutical Technology Europe.
Mattson’s group, which comprises Europe’s main pharmaceutical associations, has also helped to set up the Eco-Pharmaco-Stewardship (EPS) dealing with environmental issues during the entire lifecycles of medicines (4).
While there are big changes in both the depth and coverage of the new ERA guideline, there are also notable similarities with the 2006 document, which are already arousing opposition among NGOs and other organizations campaigning for more environmental regulatory controls on pharmaceuticals.
For many of these groups, a priority is that potential environmental damage must be included in the benefit/risk analysis by regulators when deciding to authorize a medicine. But in its revised document, EMA repeats the stipulation in its 2006 guideline that environmental impact should not ‘constitute a criterion for refusal’ of a marketing authorization (1).
“It is disappointing to see, after more than a decade, that there is no advancement in EMA’s guidelines and no stronger indication that the environmental impact of pharmaceuticals is truly being considered,” Will Clark, executive director of Health Care Without Europe, whose members include hospitals, healthcare professionals, and environmental organizations, told Pharmaceutical Technology Europe.
“ERA results should be systematically considered in the risk-benefit analysis of marketing authorization decisions for new human medicinal products,” Clark added.
NGOs have been pressing for a range of Pharmaceuticals in the Environment (PIE) controls in the EU. In 2018, the European Environmental Bureau (EEB) and Changing Markets Foundation (CMF) put forward eight pages of proposals in a joint position paper on PIE regulations, many of them linked to ERA procedures and outcomes (5).
Besides authorization of medicines being at least partly conditional on ERA results, other changes supported by NGOs include assessment of drugs authorized before the 2006 guide, incorporating assessments of manufacturing plant effluents in ERAs, and increasing public access to ERA data.
Currently, only a relatively small number of medicines have been found to pose any significant environmental risks, under the present ERA system. Out of 478 new environmental risk assessments by industry published in 2017 on the website fass.se, a Swedish medicines information portal, 10 substances were considered to pose risks or be hazardous. Two were classified as posing high-risk, seven moderate-risk, and one as being hazardous, according to a review of the assessments conducted annually by the Swedish Environmental Research Institute (IVL) (6).
Under the new guideline, more medicines may be assessed across Europe as being a potential environmental risk or hazard than under the existing guidance because of the requirement for the use of more up-to-date and in-depth test methods.
As in the 2006 document, EMA continues to advise a tiered approach to assessments of medicines with some products needing more thorough investigation than others (1).
For each medicine, both risk and hazard assessments for persistent, bioaccumulative, and toxic (PBT) substances have to be performed because harm can occur regardless of the level of exposure. But with products found not to be readily biodegradable, for example, further testing is considered necessary.
The assessment methods used with PBTs are identical to those methods that ECHA requires to be applied to chemicals under REACH (1).
A prime objective behind the more detailed guideline is the creation of more consistency on environmental risk issues between national licensing agencies. “[We are] looking for harmonization in the future, based on the implementation of the revised guideline,” Adrian van den Hoven, director general of Medicines for Europe, the generics trade association, told Pharmaceutical Technology Europe.
But harmonization may turn out to be more difficult to achieve due to the more up-to-date assessment methods advised by the guideline. The additional ERA data give more opportunities for differing interpretation of assessment information by national agency specialists. Some agencies employ their own ecotoxicologists for ERA evaluations.
NGOs are expecting that, after the consultation process on the guideline, its scope might be extended to include medicines authorized before 2006, revealing more products with environmental risks. A German report on aquatic pollution found that no ERAs on the top 10 human medicinal products found in the country’s surface water were available, according to the EEB/CMF position paper (5).
However, as part of the EPS initiative, the industry is supporting both an extension of the scope of ERA to pre-2006 products and to updating existing environmental risk assessments.
“We are investigating the methodology to prioritize legacy (pre-2006) compounds with little or no data for future ERAs,” said Mattson. “The pharmaceutical industry believes that among the large number of incompletely tested compounds for their environmental risks, only a limited number are of real environmental concern. For this (prioritization) process, no legislative initiative is foreseen yet. Therefore, a voluntary approach is more likely to go forward.”
Updates of existing ERAs would be particularly useful for companies seeking marketing authorizations of products with the same active ingredient, according to Mattson. “The oversight of this process needs to be with regulators in co-operation with industry,” he explained. “Industry is open to any non-legislative approaches (on this issue).”
Easier access to the ERA’s data of a medicine’s originator is desired, in particular, by generic-drug manufacturers. “We don’t believe that it makes sense to replicate the same studies over and over again-which would massively affect the cost and availability of generic approvals,” said van den Hoven. “No arrangement is foreseen in the current draft guideline (on data sharing), only the suggestion that sharing of information is to be considered.”
The revised guideline is likely to be changed as a result of the consultation process due to end on 30 June 2019. Also, it may have to be altered after the imminent publication of a longâawaited PIE strategy by the European Commission (7).
“If (the strategy) is released prior to the finalization of the guideline following the consultation period, (our) drafting group will attempt to align the guideline as much as possible with the Commission’s strategy,” an EMA spokesperson told Pharmaceutical Technology Europe. However, she pointed out the objectives of the two documents are different with the PIE strategy covering the full lifecycle of pharmaceuticals and the ERA guideline mainly consumption.
Nonetheless NGOs and some politicians want a much bigger overlap between the two. The 2006 document went through three consultations before being adopted. The new guideline may have to undergo at least a similar number before being finalized.
1. EMA, “Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use” (London, 15 November 2018).
2. EMA, “Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use” (London, 1 June 2006).
3. Innovative Medicines Initiative, “Intelligence-led Assessment of Pharmaceuticals in the Environment” (Brussels, 2017).
4. EFPIA and other pharmaceutical organizations, “Inter-Association Initiative (IAI), Eco-Pharmaco-Stewardship” (Brussels, April 2016).
5. European Environmental Bureau (EEB) and Changing Markets Foundation, “Policy Options for Regulating Pharmaceuticals in the Environment” (Brussels, February 2018).
6. Swedish Environmental Research Institute (IVL), “Self-Declarations on Environmental Classifications at fass.se-Experiences from Reviewing Process during 2017” (Stockholm, June 2018).
7. European Commission, “Roadmap-Strategic Approach to Pharmaceuticals in the Environment” (Brussels, 28 April 2017).
Pharmaceutical Technology Europe
Vol. 31, No. 2
When referring to this article, please cite it as S. Milmo, “Spotlight on Assessing the Environmental Impact of Medicines," Pharmaceutical Technology Europe 31 (2) 2019.