Abstract
The US Food and Drug Administration (FDA) Pregnancy and Lactation Labeling Rule (PLLR), implemented in 2015, includes information on pregnancy, lactation, and women and men with reproductive potential. To identify the drugs that have adhered to the new PLLR format; to shed light on the continued need for implementation of pregnancy, lactation, and reproduction into clinical studies; and to evaluate how many new therapeutic products have human and animal data specific to pregnancy and lactation. This cross-sectional study of 290 new therapeutic drugs reviewed labeling data for newly FDA-approved therapeutic products from January 2010 to December 2019. Therapeutic products submitted on or after June 30, 2015, were required to be in PLLR format; those approved from June 30, 2007, to June 29, 2015, had until June 30, 2019, to be in PLLR format. Approval data and subsequent labeling revision were evaluated for pregnancy and lactation data (human and animal), pregnancy registry, black-box warnings, and inclusion of PLLR labeling format. Date of new drug approval by FDA. Compliance with PLLR; presence of animal or human data; presence of pregnancy registries; and presence of information regarding female and male reproductive potential. A total of 290 new molecular entities or therapeutic products were approved by the FDA between 2010 and 2019 in 19 categories. Black-box warnings occurred in 89 drugs (30.7%; 95% CI, 25.4%-36.3%), with 3 (3.4%; 95% CI, 0.7%-9.5%) involving pregnancy. All products submitted after June 30, 2015, were in PLLR format; however, of the 138 submitted between 2010 and that date, 45 (32.6%; 95% CI, 24.9%-41.1%) were not in PLLR format by June 30, 2019. During the 10 years of data analyzed, significantly more were in PLLR format (P for trend < .001). Most approved therapeutic products have pregnancy data derived from animal studies (260 products; 89.7%; 95% CI, 85.6%-92.9%) but only 31 (10.7%; 95% CI, 7.4%-14.8%) derived data from human studies. Only 148 therapeutic products (51.0%; 95% CI, 45.1%-56.9%) had any data associated with lactation, 143 (49.3%; 95% CI, 43.4%-55.2%) originating from animal studies and 8 (2.8%; 95% CI, 1.2%-5.4%) from human studies. The results of this study show that with the implementation of PLLR in the last decade, new therapeutic products were in compliance with the new rules; however, more than one-third of labels remain out of PLLR compliance. Human data on pregnancy and lactation are available in less than 20% of new product labeling.
Highlights
Most women will take at least 1 medication during pregnancy, delivery, or the postpartum period.[1,2] To inform patients on the safety and efficacy of these therapies used during pregnancy and postpartum, obstetrical care professionals rely on available information
The introduction of a new Food and Drug Administration (FDA) labeling requirement was posted in the Federal Register in 2008, which would eventually become the implementation of the Pregnancy and Lactation Labeling Rule (PLLR) in 2015.4,5 The change in the labeling process transitioned from the initial letter grade pregnancy category to a more structured approach
We have 3 aims in this study, as follows: (1) to identify the drugs that have adhered to the new PLLR format; (2) to shed light on the continued need for implementation of pregnancy, lactation, and reproduction in clinical studies; and (3) to evaluate how many new therapeutic products have human and animal data specific to pregnancy and lactation
Summary
Most women will take at least 1 medication during pregnancy, delivery, or the postpartum period.[1,2] To inform patients on the safety and efficacy of these therapies used during pregnancy and postpartum, obstetrical care professionals rely on available information. The FDA evaluates new and existing medications and provides recommendations regarding safety, during pregnancy and lactation These recommendations were initially provided in the late 1970s, with the development of the alphabetic risk stratification system (ie, A, B, C, D or X, with A indicating adequate and well-controlled studies have proven safety in pregnancy and X indicating that studies have shown human fetal risk if ingested during pregnancy).[3,4] This approach was designed to convey the type and amount of data that were available at the time. The subsection on women and men with reproductive potential includes information regarding pregnancy testing, contraception, and infertility as it relates to the drugs, when necessary.[4]
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