Regulators Seek More Drug Effects Research Related to Pregnancy, Lactation

Initiatives to learn more about the impact of drugs and medical products on diverse population groups is driving efforts to assess the effect of medicines and vaccines on pregnant and lactating patients. The aim is to expand and clarify methods for obtaining information on medicines used by or needed for this population through clinical trials and postapproval studies, as seen in a number of policy initiatives and expert assessments of ways to obtain reliable information on how drugs affect these patients.

Pregnant women traditionally have been excluded from preapproval studies due to concerns about potential damage to the health of the mother and the fetus. Unfortunately, that has created a serious dearth of useful information on safe treatments for this group, including individuals coping with serious conditions. While FDA has required sponsors to include in labeling available information on drug impact for this population, the agency does not require research sponsors to collect such data in clinical trials.

Yet the ongoing interest in including more pregnant and lactating women in clinical trials continues to generate research and strategies on the subject, as presented at a recent workshop on the issue organized by the Forum on Drug Discovery, Development and Translation at the National Academy of Sciences, Engineering and Medicine (NASEM).¹ The program in mid-June examined the ethical issues and gaps in treatment information due to the exclusion of this population from clinical research. Experts reviewed the laws and regulations governing R&D for pregnant and lactating persons, along with opportunities to improve evidence on the risks and benefits of drug products for these patients. A report will be issued on strategies for overcoming barriers to clinical research, for addressing liability concerns, and short- and long-term proposals for moving forward.

More real-world data

Meanwhile, FDA has encouraged pregnant and lactating women to join registries that collect information on exposure to drugs and vaccines during pregnancy and after.² And more recently, the agency and researchers have explored how broader use of real-world data (RWD) and postapproval studies can enhance understanding on the impact of drugs on pregnant and lactating women. This topic was the focus of a workshop organized by Johns Hopkins in May, where experts examined strategies for leveraging real-world evidence (RWE) to study medication use in pregnancy and lactation.³

FDA also seeks to revise draft guidances issued in 2019 on how researchers can obtain information on drug effects on pregnant and lactating women through pharmacovigilance programs, electronic health record data systems, surveillance programs, and the broader use of RWD to inform the safety of drug use for this population.⁴ A related draft guidance describes how drugmakers should conduct clinical lactation studies for drugs likely to be used in women in this situation.⁵

Seeking global standards

This issue, moreover, has gained international attention as part of efforts to advance research on women in a wider range of health conditions. The International Council on Harmonization (ICH) agreed at its May meeting in Athens to add this topic to its list of issues warranting global standards. A proposal developed by officials at FDA, the European Medicines Agency (EMA), and the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) calls for developing a new ICH efficacy guideline on a global framework for including pregnant and breastfeeding individuals in clinical trials.⁶ The aim is to benefit this often ignored population and to better inform providers and the global pharmaceutical industry.

Of note, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) recently said it was updating its system for providing advice on use of drugs for pregnant and breastfeeding women. This involves expanding its registry and information system to improve data collection and to provide speedy consultations through online systems tracing the effects of medicines on this population.⁷

Many of these initiatives build on the report issued in 2020 by the national Task Force on Research Specific to Pregnant and Lactating Women (PRGLAC), which was initiated by the 21st Century Cures Act of 2016 to address gaps in knowledge and research on this topic. That panel called for broader pregnancy registries, more research on treatments for this group, design of studies for timely collection of relevant data, and linking health records of mothers and children to address these issues.⁸ 

And biopharma companies agreed in the latest Prescription Drug User Fee Act plan (PDUFA VII) to support efforts to determine what data and post-market safety signals best indicate exposure to medication in pregnancy and how that may help assess the effects of drugs and vaccines in pregnant women. FDA will explore the use of pregnancy registries and electronic health record systems in establishing a standardized process for this purpose at a public workshop that through demonstration projects and issue a proposed framework and guidance by 2027.⁹

References

1. https://www.nationalacademies.org/event/06-16-2022/inclusion-of-pregnant-and-lactating-persons-in-clinical-trials-a-workshop
2. https://www.fda.gov/science-research/womens-health-research/list-pregnancy-exposure-registries
3. https://www.jhsph.edu/research/centers-and-institutes/center-of-excellence-in-regulatory-science-and-innovation/news-and-events/FDA%20OWH-CERSI-Collaborative-Workshop.html
4. https://www.fda.gov/media/124746/download
5. https://www.fda.gov/media/124749/download
6. https://www.ich.org/pressrelease/press-release-ich-assembly-hybrid-meeting-athens-may-2022
7. https://www.pmda.go.jp/files/000246799.pdf#page=10
8. https://www.nichd.nih.gov/sites/default/files/inline-files/PRGLAC_Implement_Plan_083120.pdf
9. https://www.fda.gov/media/151712/download