08/11/2025
Photo by Suhyeon Choi on Unsplash
On June 4th, 2025 the European Medicines Agency (EMA) posted a guideline from the International Council for Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) titled: ICH E21 Guideline on inclusion of pregnant and breastfeeding individuals in clinical trials. Individuals who are pregnant or breastfeeding make up a significant portion of the world’s population, however, the European Union (EU) reports that less than 0.4% of clinical trials currently submitted to the EU include pregnant people and only 0.1% include lactating individuals. This guideline highlights the importance of including these individuals as well as the steps that should be taken in order to ensure their safety during a trial.
The guideline starts with the background of pregnant and breastfeeding individuals in clinical studies, the general principles and why we should adapt studies to promote their inclusion, as well as ethical considerations that must be considered rooted in the Declaration of Helsinki and ICH E6(R3) & E8(R1) guidelines. For pregnant individuals, this section of the guideline is considerably longer as there is greater concern for the immediate health and safety of both the mother and fetus. During the trial development stage, sponsors should consider the following:
How might pregnancy affect the disease state for the targeted condition?
Is there any existing evidence that would support the inclusion of pregnant individuals?
Do safety concerns and potential risks identified in existing data outweigh the potential benefit to the pregnant individual?
Should a sponsor decide to go ahead with inclusion pregnant individuals, many aspects of the trial may need to be adapted in order to protect the rights, safety, and welfare of these individuals. These aspects include, but are not limited to:
Safety Monitoring: Pregnant individuals who are enrolled into the study must be closely monitored throughout the study for any pregnancy related adverse events. There should also be an informed management plan of how to proceed should one of these events occur to ensure the safety of both the mother and fetus.
Patient Recruitment: While the general principles for patient recruitment outlined in ICH E6(R3) are still applicable, it is important to also keep in mind that pregnant individuals may have enhanced social and/or family interests during this time that could influence their autonomy. This could unduly encourage or deter them from participating in clinical trials which can result in lower recruitment rates for these individuals. The guideline recommends providing more detail about the proposed study and how it may impact future pregnant individuals to help ease any concerns.
The informed consent process: The consent form should reflect the benefits and risks of the investigational product in the intended trimester of pregnancy. It should also be made clear to the patient and their health care provider how the study procedures will be handled in the case of delivery during the study and that clinical care will always take precedent over the study.
The following section in the guideline for breastfeeding individuals contains all the same sections with more of a focus, especially during trial development, on how the investigational product transfers into breastmilk and how it would affect a child receiving it.
The full guideline is available on the EMA website as well as on the US Food and Drug Administration’s (FDA) website who also posted the guideline in July, 2025, both are currently open for comments. Comments to the EMA are due September 15, 2025 and the FDA on September 19, 2025. The FDA also posted a draft guidance for industry from 2018 titled “Pregnant Women: Scientific and Ethical Considerations for Inclusion in Clinical Trials” which covers many of the same topics. For more information have a look at our 3-part blog series (Part 1, Part 2, Part 3) where we covered the draft guidance and its contents in extensive detail and see how it compares to this new E21 guideline. While you are there, sign up for our free blog and newsletter to stay up to date on clinical trial related new such as this!
-The Clinical Pathways Team
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