From EMA for Pharma SMEs: Updated User Guide

Wien, 15.02.2024 – Text: Catarina Carrão

On the 23rd of January 2024, the European Medicines Agency (EMA) released a major revision of its user guide for micro, small and medium-sized enterprises (SMEs) in the pharmaceutical sector. The revised guide offers a comprehensive view on the European Union (EU) legislative framework for medicines, outlining requirements for the development and authorization of medicines for human use. Take a look at the new important sections/sub-sections…

Clinical Trials Information System (CTIS)

There is an extensive chapter providing an overview of the clinical trial regulation and Clinical Trials Information System (CTIS), which now harmonises the assessment and supervision of clinical trial applications throughout the EU/EEA member states. Each member states retains the responsibility for the trial, while EMA is responsible for the maintenance of CTIS, and the European Commission (EC) ensures oversight and control of the implementation of the Clinical Trials Regulation.

CTIS has become the single-entry point for the submission, supervision, and authorisation of clinical trial applications for human medicines in the EU/EEA, with secure workspaces forsponsors and authorities, including a public website to search for information on clinical trials. Deferral procedures can apply, under which sponsors can request a deferral of certain information related to the clinical trial in the public domain.

CTIS together with other EMA IT tools also supports the coordinated assessment of safetyreporting in clinical trials. SMEs should be aware that if the final formulation differs from that of the IMP used in earlier clinical trials, the relevance of the earlier material compared to the product tested in later phases should be described. Special consideration should be given to changes in quality parameters with potential clinical relevance ( vitro dissolution rate).

Borderline products

The new user guide offers advice on borderline products which have regulatory framework uncertainty. Such products englobe medicinal products, medical devices, cosmetics, biocidal products, herbal medicines, and food supplements. National competent authorities classifyborderline products either as medicinal products or, for example, as medical devices on a case-by-case basis, and this determines the applicable regulatory framework. Applicants who are unclear on the correct classification of their product, should consult a national competent authority and provide information on the product’s composition, constituents, mode of action and its intended purpose. If scientific questions arise, then EMA’s Innovation Task Force (ITF) can give further support.

Environmental Risk Assessment (ERA)

This new sub-chapter defines requirements to investigate potential environmental risks of a medicinal product following its use in patients. The ERA is mandatory for all marketing authorisation applications, although in some cases it can consist of a justification for not submitting data. As such, this evaluation is now a stepwise approach. The first part of theinvestigation estimates the exposure of the environment to the active substance and thepotential for bioaccumulation, and persistence in the environment. As such, based on an action limit, the assessment of environmental risk may be terminated at this stage. Above this limit, the fate of the substance in the environment and its associated effects should be investigated in a second phase of investigation. Some product classes (e.g., endocrine active agents) require this second part irrespective of the predicted environmental exposure.

How to use big data for decision making

In the context of medicines regulation, big data includes real world data such as electronic health records, registry data and health insurance data, pooled clinical trials data, datasets from spontaneously reported suspected adverse drug reaction reports, and genomics, proteomics, and metabolomics datasets. In line with the agency regulatory strategy for 2025 and the European Medicines Regulatory Framework (EMRF), the aim is to establish a better integration of Real-World Data (RWD) and Real-World Evidence (RWE). As such, alongside the gold standard of controlled trials, the wish of EMA is to include RWD/RWE into regulatory decisions on the development, authorisation, and supervision of medicines. Projects are being piloted as we speak, to enable the use and establish the value of RWE, and individual patient data from clinical trials.


This procedure is designated to support the access to high-priority medicines for patients outside of the EU. Products eligible for this procedure include for example vaccines used in the World health organization (WHO) Expanded Programme on Immunization, or for protection against a public health priority disease, as well as medicines for WHO target diseases such as HIV/AIDS, malaria, dengue, and tuberculosis. Cooperation with WHO and regulators from countries where the products are expected to be used, enriches the epidemiology and local disease expertise, facilitates a benefit-risk assessment tailored to the intended non-EU population, streamlines the WHO prequalification programme, and facilitates national registration in target countries. As such, EMA welcomes parallel applications for a centralised EU marketing authorisation and an opinion under the EU-M4all pathway. For a medicine to be eligible for a parallel evaluation, the active substance(s) must be identical in both applications, with comparable indications, although the formulation, pharmaceutical form or route of administration may be different in the two applications.

The “OPEN” Initiative

EMA collaborates with medicines regulators outside the EU in the scientific evaluation of certain medicines, within a framework called ‘OPEN’ (opening procedures at EMA to non‑EU authorities). Within this framework, several regulators evaluate a medicine in parallel with EMA, remaining scientifically and procedurally independent from one another while sharing information, expertise, and approaches during the evaluation. The WHO is a partner in the initiative, which aims to accelerate registration and availability of certain medicines in low- and middle-income countries.

Image: Stock Photo

Further Reading:

All references assessed 15 February 2024.



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