Jun 12, 2025
Introduction
Pregnant and breastfeeding individuals have long been excluded from clinical research—an exclusion rooted in historical ethical concerns and perceived risk. Yet this protective stance has unintentionally led to a dangerous information gap: most drugs on the market lack sufficient data to guide safe and effective use during pregnancy or lactation.
The newly released ICH E21 guideline offers a framework to change this. It aims to standardize global efforts to include and retain pregnant and breastfeeding participants in clinical trials when scientifically and ethically appropriate—supporting more equitable, evidence-based care.
What’s Missing in Current Clinical Research
Today, most clinical trials exclude pregnant individuals outright, even when the drug in question is likely to be used by this population after approval. As a result:
Over 90% of medications approved in the U.S. between 2000 and 2010 lack pregnancy-specific safety data.
Drug labels often provide warnings but little actionable guidance for clinicians treating pregnant patients.
Dosing regimens are rarely optimized for pregnancy, despite known physiological changes that alter how drugs are processed in the body.
Post-marketing surveillance systems are inconsistent and underutilized, limiting the ability to gather real-world safety data.
This lack of evidence contributes to unnecessary risk, conservative treatment decisions, and missed opportunities for intervention—especially in chronic, infectious, and life-threatening conditions where medication use during pregnancy is unavoidable.
What the ICH E21 Guideline Recommends
ICH E21 outlines a science-based, ethically grounded approach to improving inclusion of pregnant and breastfeeding people in clinical development. The guideline recommends:
Evaluating whether inclusion is scientifically appropriate as early as possible in the development lifecycle.
Replacing automatic exclusion with careful, dynamic risk-benefit assessments based on available data and the potential for therapeutic use in pregnancy.
Designing trials that include appropriate safety monitoring and tailored consent processes.
Using supplemental data sources, including registries, modeling, and post-marketing surveillance to strengthen findings.
Promoting regulatory harmonization across regions to support global alignment in ethics and expectations.
This shift moves the industry away from blanket exclusion and toward a more thoughtful, transparent standard that protects participants while enabling better data generation.
The Role of Biopharma and Clinical Teams
Implementing ICH E21 will require collaboration across the drug development ecosystem. Biopharmaceutical sponsors, CROs, and site investigators must work together to evaluate when and how to include pregnant individuals, develop appropriate protocols, and align with ethics boards and regulators on safe participation.
This guidance also has strategic implications. As regulators move toward global alignment on inclusion standards, companies that proactively address these expectations will be better positioned for smoother approvals, stronger safety data, and broader access post-launch.
Conclusion
The historical exclusion of pregnant and breastfeeding individuals from clinical trials has left a significant evidence gap in how we treat one of the most medically vulnerable populations. The ICH E21 guideline marks a necessary turning point—one that prioritizes equity, scientific rigor, and ethical responsibility.
At Pharmefex, we support our clients in adapting to evolving regulatory landscapes like ICH E21 through strategic guidance, regulatory insight, and cross-functional compliance planning. Together, we can drive a more inclusive and evidence-informed future for drug development.