Revised guideline to assess risk of human medicines for the environment

EMA has published a Draft guideline on the environmental risk assessment of medicinal products for human use - Revision 1for a six-month public consultation. Stakeholders are invited to send their comments by 30 June 2019 to era_dg@ema.europa.eu using the

provided.

The presence of biologically-active pharmaceuticals in the environment is a growing concern, because some of these substances have shown direct effects on wildlife at or below the concentrations found in water and soil. For example, male fish exposed to the main ingredient in the contraceptive pill may become feminised and this can affect the capacity of the population to reproduce. Pharmaceuticals may also have indirect effects e.g. a recent study shows that pharmaceutical compounds detected in surface waters can transfer from invertebrate larvae to the predators that feed on them.

Human medicines may enter the environment during their manufacture, use and disposal. The ERA is based on the use of the product and the physico-chemical, ecotoxicological and fate properties (degradation, persistence) of its active substance.

Environmental risk assessment of medicines ensures that the potential effects of pharmaceuticals on the environment are studied and that adequate precautions are taken in case specific risks are identified. Performing an ERA is mandatory for any pharmaceutical company submitting a marketing authorisation application for a medicine, regardless of the type of medicine. Appropriate details are included in the European Public Assessment Report (EPAR) of approved medicines, so that this information is available to the public.

The revision of EMA’s guideline on ERA introduces a decision tree clarifying when ERA studies are required and provides more detailed technical guidance to applicants to increase the consistency of the assessments.

One of the most notable changes introduced in the proposed revision is the introduction of the term ‘endocrine active substances’, to include all compounds that affect development or reproduction. Additionally, guidance is provided for the estimation of the exposure of predators to pharmaceuticals through the food chain (‘secondary poisoning’), as well as directly through the environment. The revision also proposes to limit the use of a laboratory test method - the Organisation for Economic Co-operation and Development (OECD) 308 environmental fate test - to certain categories of substances and this will reduce the burden of testing on applicants.

The revision of the ERA guideline is based on a concept paper issued in 2014 and the work of a group of experts led by the Safety Working Party of EMA’s Committee for Medicinal Products for Human Use (CHMP)">human medicines committee (CHMP). It builds on the twelve years of experience gained since the original guideline was published and aims to facilitate the work for both applicants and regulators in the interest of environmental protection.

In the interest of animal welfare, the guideline encourages applicants to share data generated for the ERA, implementing the principles of 3Rs (Replacement, Reduction and Refinement) - in accordance with Directive 2010/63/EU - to avoid unnecessary repetition of studies.