FDA seeks global shift to include pregnant women in medical research

Regulatory NewsRegulatory News
| 21 July 2021 | By Mary Ellen Schneider 

Lynne Yao, MD

The COVID-19 pandemic has put a spotlight on the paradox surrounding the inclusion of pregnant and breastfeeding women in medical research. Even when these women are at higher risk for severe illness and hospitalization, they are unlikely to be included in clinical trials for medical products and vaccines.

In a recent article, officials at the US Food and Drug Administration (FDA) signaled their commitment to work with industry and other regulators to support the inclusion of pregnant and breastfeeding women in medical research across the globe, not just for COVID-19 but for a range of common and serious conditions like asthma, epilepsy, and depression.

“Developing a roadmap for change, through international cooperation and harmonization, will take much care, consideration, and communication between all stakeholders,” the officials wrote in an FDA Voices article. “Despite persistent challenges, there is strong interest from the international regulatory community to continue the momentum in this important area of women’s health.”

Lynne Yao, MD, director of pediatric and maternal health in FDA’s Center for Drug Evaluation and Research, and a co-author of the FDA Voices article, told Focus that the agency “intends to support various efforts to improve information on the safe use of medicines in pregnancy and during lactation.”

Yao said FDA is “actively reviewing comments” received for three draft guidance documents issued in 2018 and 2019 on study design for clinical lactation studies, post-approval pregnancy safety studies, and scientific and ethical consideration for inclusion of pregnant women in clinical trials. (RELATED: FDA Drafts Guidance on Scientific and Ethical Considerations in Including Pregnant Women in Clinical Trials, Regulatory Focus 06 April 2018; Studying Drugs in Pregnant and Nursing Women: FDA Issues Draft Guidances, Regulatory Focus 08 May 2019)

“Additionally, FDA continues to engage with external stakeholders to advance inclusion of pregnant and breastfeeding patients in clinical research,” said Yao.

For instance, FDA, the European Medicines Agency (EMA) and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) presented information on inclusion of pregnant and breastfeeding women in trials during the Drug Information Association annual meeting in June 2021. FDA officials are also planning to participate in the American College of Clinical Pharmacology annual meeting in September 2021, which includes discussions on the enrollment of pregnant women in clinical pharmacology trials and the transfer of drugs into breastmilk.

Challenges & US Actions

The COVID-19 pandemic highlighted some of the challenges in moving this area forward. COVID-19 infection places pregnant women at increased risk for serious obstetrical complications, including preterm birth, with but no pregnant women were enrolled in clinical trials of the COVID-19 treatment remdesivir or any of the pivotal trials of COVID-19 vaccines run by Pfizer-BioNTech, Moderna, or Janssen, the vaccines arm of Johnson & Johnson. This was despite encouragement from FDA to include pregnant women in prelicensure COVID-19 vaccine trials.  

Concerns over the potential risk to the fetus or child have effectively blocked pregnant and breastfeeding women from participating in pre-approval clinical trials, leading to a lack of data on the safety and effectiveness of treatments for this population. FDA began to tackle the issue of lack of data in 2014 with the finalization of the Pregnancy and Lactation Labeling Rule, which required manufacturers to keep drug labels updated with any information relevant to pregnant or breastfeeding women. But FDA officials noted that the agency stopped short of requiring the collection of these data through clinical trials or studies.

Following that initial effort, FDA rolled out its series of draft guidance documents in 2018 and 2019. Pregnant and breastfeeding women were also part of FDA’s late 2020 final guidance on diversifying clinical trial populations. For instance, FDA urged industry to consider including pharmacokinetic sampling to establish dosing in women who become pregnant during a trial (when it is safe to do so), a step that would provide critical information on drug metabolism during pregnancy. (RELATED: FDA lays out strategies for promoting diversity in clinical trial enrollment, Regulatory Focus 09 November 2020)

FDA was also part of the Task Force on Research Specific to Pregnant and Lactating Women (PRGLAC) that released an implementation plan in 2020 calling on industry to explore alternative trial designs that would better accommodate pregnant and breastfeeding women.

Global Efforts

US regulators are not the only ones highlighting the lack of data on the safety and efficacy of medicines for pregnant and breastfeeding women. The Continuum of Evidence from Pregnancy Exposures, Reproductive Toxicology and Breastfeeding to Improve Outcomes Now (ConcePTION) was launched in 2019 in Europe as a public-private partnership to raise awareness of the information gap for this population. The group has called for improving and combining existing pregnancy registries as one way to gain more data.

EMA has also indicated its intention to make inclusion of pregnant and breastfeeding women into clinical trials one of the core recommendations in its 5-year strategic plan.

In February 2021, regulators from FDA, EMA, and MHRA published an article in Clinical Pharmacology & Therapeutics outlining their shared approach to ensuring access to safe medicines for pregnant and breastfeeding women, including:
  • Approaching the use of medicines in pregnancy and breastfeeding from a benefit-risk perspective
  • Evaluating new approaches to nonclinical reproductive toxicology
  • Systematic consideration of possible use of medicines by pregnant and breastfeeding women
  • Addressing regulatory and liability barriers to clinical trial inclusion
  • Supporting clinical decisions, rational use, and appropriate dosing through systematic and timely study of medicines likely to be used in this population
  • Examining the regulatory system to ensure timely and efficient use of all available data resources
  • Challenging industry and researchers to partner globally to develop robust electronic data collection and analysis
FDA Voices article on Pregnant and Breastfeeding Women in Clinical Research


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