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. 2020 Aug 3;3(8):e2015094.
doi: 10.1001/jamanetworkopen.2020.15094.

Evaluation of Drug Labels Following the 2015 Pregnancy and Lactation Labeling Rule

John J Byrne  1 , Alexander M Saucedo  1 , Catherine Y Spong  1
Affiliations

Evaluation of Drug Labels Following the 2015 Pregnancy and Lactation Labeling Rule

John J Byrne et al. JAMA Netw Open. .

Abstract

Importance: 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.

Objectives: 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.

Design, setting, and participants: 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.

Exposures: Date of new drug approval by FDA.

Main outcomes and measures: Compliance with PLLR; presence of animal or human data; presence of pregnancy registries; and presence of information regarding female and male reproductive potential.

Results: 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.

Conclusions and relevance: 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Byrne reported receiving an honorarium from Obstetrics and Gynecology outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Association of the Pregnancy and Lactation Labeling Rule (PLLR) With Drug Labeling
The number of new products approved by the FDA ranged from 14 (2010, 2016) to 44 (2018). All products submitted after June 30, 2015, were in PLLR format; however, of those submitted between 2010 to 2015, 45 of 138 (32.6%) were not in PLLR format by the designated date of June 30, 2019. The percentage that included a pregnancy registry ranged from 0% to 25%.
Figure 2.
Figure 2.. Pregnancy and Lactation Data Derived From Human and Animal Studies Before and After Implementation Date
The amount of human and animal data for pregnancy and breastfeeding ranged from year to year. The amount of pregnancy and lactation-specific data derived from human research ranged from 0% to 28% and 0% to 8%, respectively. The amount of pregnancy and lactation-specific data derived from animal research ranged from 79% to 100% and 39% to 68%, respectively. The Pregnancy and Lactation Labeling Rule (PLLR) was implemented June 30, 2015.
Figure 3.
Figure 3.. Products With Female and Male Reproductive Potential Category
Products with data in the female and male reproductive potential subsection by year as compared with therapeutic products in Pregnancy and Lactation Labeling Rule (PLLR) format. The PLLR was implemented June 30, 2015, and is highlighted on the figure.
See this image and copyright information in PMC

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