Clinical trials have long shaped the future of medicine. But for decades, one vital population has remained mostly sidelined: pregnant and breastfeeding individuals. Now, that’s changing.
With the release of the ICH E21 Draft Guideline, global health regulators have taken a bold step to encourage the safe, ethical, and proactive inclusion of pregnant and breastfeeding people in clinical research. This guideline, now under public consultation, marks a significant move toward equity, scientific rigor, and public health protection.
Why This Guideline Matters
Millions of people who are pregnant or breastfeeding manage chronic and acute conditions — from autoimmune disorders to infections and mental health issues. Yet, they are often excluded from drug trials, leading to a lack of evidence to guide treatment during these critical life stages.
Without this data:
- Healthcare providers may avoid essential treatments.
- Patients may receive inappropriate dosing.
- Breastfeeding might be discouraged due to unknown risks.
- Harmful or ineffective treatments may be used unknowingly.
The ICH E21 guideline aims to fix this evidence gap with structured, science-backed recommendations.
Key Goals of the ICH E21 Guideline
- Inclusion by Design: Clinical trial planning should account for the needs of pregnant and breastfeeding populations from early development through post-approval.
- Risk-Benefit Evaluation: Inclusion should be based on a “weight-of-evidence” approach — combining nonclinical data, safety profiles, and potential benefits.
- Flexible Consent and Safety: Trials must ensure informed consent and minimize risks to both the individual and their baby.
- Real-World Data Use: Post-marketing surveillance and real-world evidence are vital to understanding long-term effects and rare outcomes.
What’s New for Pregnancy in Clinical Trials?
The guideline emphasizes that pregnancy is not a contraindication by default. Instead, the decision to include pregnant individuals should be:
- Driven by medical need.
- Informed by nonclinical (animal) studies and early human data.
- Based on the product’s potential impact during different trimesters.
Sponsors are encouraged to plan for:
- Tailored study designs (e.g., PK/PD studies during pregnancy).
- Risk mitigation strategies.
- Tracking fetal exposure and neonatal outcomes.
Importantly, if a participant becomes pregnant during a trial, there should be options for continued participation with proper safeguards and re-consent.
Considerations for Breastfeeding Individuals
The guideline outlines a structured approach:
- Assess drug transfer into breast milk.
- Estimate infant exposure and potential risks.
- Evaluate the impact on breastfeeding itself (e.g., milk production).
Breastfeeding participants may be included if:
- The investigational product poses minimal risk to the infant.
- The infant may also benefit from exposure (e.g., immune conditions).
Protocols should allow flexibility — such as pumping and discarding milk — and provide lactation support to help participants continue breastfeeding safely.
Ethical and Practical Challenges
Including these populations raises complex ethical and logistical challenges. The guideline addresses:
- The importance of IRBs/Ethics Committees with relevant expertise.
- Strategies for respectful and culturally sensitive recruitment.
- Minimizing procedural burdens (e.g., virtual visits, aligned check-ups).
- Clear communication of potential risks and benefits.
What This Means for the Future
This guideline represents a cultural shift in research — one that recognizes the autonomy, needs, and rights of pregnant and breastfeeding people. By fostering their inclusion, the scientific community can close longstanding knowledge gaps, ensure safer treatments, and better protect both parents and children.
Get Involved
The ICH E21 Guideline is currently open for public consultation until 15 September 2025. Researchers, healthcare professionals, patients, and advocates are encouraged to review and submit feedback to help shape its final form.
