Big Changes in European Pharma Legislation

New Pharmaceutical Legislation and updates to Environmental Risk Assessments herald a more integrated regulatory system 

The European pharmaceutical legislation is currently being revised to a format intended to be future-proof. The New Pharmaceutical Legislation (NPL), as it is called, is expected to enter into force later in 2026, with a two-year transition period. In this interval, all EU Member States will need to update their national laws to align with the new rules, while the European Commission, EMA and EU Member States will provide implementation guidance to stakeholders.

The NPL revises and replaces two decades of existing general pharmaceutical legislation (Regulation (EC) No 726/2004 and Directive 2001/83/EC) and the legislation on medicines for children and for rare diseases (Regulation (EC) No 1901/2006 and Regulation (EC) No 141/2000, respectively), and it is awaiting approval by the European Parliament and the Council.

Why this review is necessary?

Over the past 20 years, there has been growing concern about patients' access to medicinal products. This has been due to shortages across many EU countries. In addition, it appeared that access to innovative medicinal products and promising therapies varied across the EU.  Concerns regarding antimicrobial resistance and the environmental impact of medicinal products needed more attention, as did simplifying the authorizations system. The objective of the NPL is therefore to create a more integrated regulatory system to support medicine developers by reducing administrative burden, improving the sustainability of the European medicines network, and optimizing the use of scientific resources, leading to more agile medicine assessments. The NPL also puts the spotlight on the environment by focusing on the impact of medicines on the environment and the prudent use of drugs with an antimicrobial mode of action.

Environmental Risk Assessment: A more prominent role in Marketing Authorization Application

Among the important changes proposed in the updated legislation is the approach to the Environmental Risk Assessment (ERA) of medicinal products, including:
•    A proposal to create an ERA Monograph system per active substance, including a comprehensive set of physico-chemical, fate, and effect data based on an assessment of a competent authority. Upon the decision of the Commission, the ERA monographs can be used in the context of new marketing authorisation applications for medicinal products to support their own ERA.
•    Generic pharma companies are also encouraged to conduct joint studies or reuse animal study results from existing ERAs, in line with 3Rs principles and to avoid duplication of animal testing.
•    Data generated via in silico methods, such as computational modelling and simulation, molecular modelling, mechanistic modelling, digital twin and artificial intelligence, where appropriate, could also be used to support regulatory decision-making.
•    For medicinal products authorized before 2005, EMA will establish a risk-based prioritization program for submission or update of the ERAs by the market authorisation holders.
•    The scope of the ERA will be extended to cover new protection goals as antimicrobial resistance during the entire life cycle of a drug medicine (including manufacturing). Risk Mitigation Measures (RMM) should also be included in the Marketing Authorization Application.
•    Medicinal products containing an active substance which is persistent (or very persistent), bioaccumulative (or very bioaccumulative), mobile (or very mobile) and toxic should be subject to medical prescription.

One important point of attention is that in case an environmental risk assessment is incomplete, insufficiently substantiated or if the identified risks are insufficiently addressed by the applicant, the marketing authorization will be turned down, unless the applicant has duly justified and substantiated the reasons for the incomplete or insufficiently substantiated ERA, and the competent authorities consider that the marketing authorisation can be granted subject to post-authorisation commitment to provide additional studies or to implement risk mitigation measures. This is in sharp contrast with the current legislation, under which the identified environmental risks cannot constitute a major objection to the marketing authorization. This emphasizes the increased focus on the environmental impact of medicines in Europe and underscores the need for pharmaceutical companies to ensure that potential environmental risks associated with their medicinal products are adequately investigated and mitigated. 

The Agency shall draw up scientific guidelines specifying technical details regarding the ERA requirements for medicinal products for human use, including antimicrobials other than antibiotics.

No time to waste

The Environmental Risk Assessment of drug medicines can be a lengthy and complex process, involving long-term studies (e.g.: long-term aquatic and environmental fate studies) and can take several years depending on the product and the target market. In the context of the New Pharmaceutical Legislation, it is essential to be prepared in advance and make sure the ERA is conducted in an appropriate and timely manner prior to the Marketing Authorization Application.

Charles River experts at Regulatory Affairs stay up to date with the latest developments concerning the New Pharmaceutical Legislation and Environmental Risk Assessment for drug medicinal needs. With many years of experience dealing with these assessments and related testing [Environmental Risk Assessment for Pharmaceuticals | Charles River] CRL offers the necessary experimental and regulatory support to your Marketing Authorization Application.

Thais Muniz, MSc, is Section Head of Regulatory Environmental Toxicology and Chemistry within Charles River's Safety Assessment business.