On Monday, July 21, 2025, the Food and Drug Administration (FDA) issued draft guidance entitled "E21 Inclusion of Pregnant and Breastfeeding Women in Clinical Trials" from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). The guidance is currently in Step 2 of the ICH process and open for public comment until September 19, 2025.
The draft guidance outlines regulatory expectations for the inclusion of pregnant and breastfeeding women in clinical trials across the product lifecycle. It also addresses study design, benefit-risk assessment, pharmacokinetic modeling, and ethical considerations specific to pregnant and breastfeeding participants, encourages early planning for inclusion of these populations, discusses conditions under which contraception requirements may no longer be necessary, and proposes approaches for allowing participants to remain in trials after becoming pregnant.
The publication of the draft guidance follows the FDA's removal of draft guidance on clinical trial diversity from their website in late January 2025. The current ICH document focuses specifically on sex-based inclusion in the context of pregnancy and breastfeeding. It does not address racial or ethnic diversity or reference prior domestic guidance withdrawn during the Trump Administration.
Recent public statements by FDA officials have also emphasized women's health as a renewed area of interest. On an edition of the FDA Direct podcast published on July 16, 2025, members of FDA leadership discussed the scientific and regulatory considerations around hormone replacement therapy (HRT). Dr. Marty Makary, FDA Chief Medical Officer and Director of the Center for Biologics Evaluation and Research (CBER), questioned longstanding concerns about breast cancer risk and noted emerging evidence supporting cardiovascular, cognitive, and skeletal benefits of HRT when initiated near the onset of menopause. FDA leadership confirmed that the FDA plans to convene a new expert panel to reexamine HRT evidence, characterizing prior policy responses as overly cautious.
These developments suggest that women's health, including conditions related to pregnancy, lactation, and menopause, may become a more prominent area of regulatory focus. While the draft guidance does not address menopause or HRT directly, the broader context indicates increasing agency attention to sex-specific research gaps and long-term safety data. The draft guidance also reflects a continuing emphasis on harmonized regulatory expectations and data generation for historically underrepresented populations.
It remains to be seen how the FDA will operationalize the draft guidance in regulatory review. Stakeholders may prioritize evaluating whether current trial designs, particularly those involving pregnant or breastfeeding women, are aligned with the expectations described in the draft guidance. This may include reviewing contraception requirements, approaches to handling pregnancies during trials, and data collection related to maternal and infant outcomes.
The FDA has not issued an implementation timeline or companion guidance. Crowell and Crowell Health Solutions will continue to monitor for additional guidance and announcements.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.
