P35: FDA Postmarketing Requirements in Pregnant and Lactating Women: Past, Present, and Future
ORISE Fellow, ORDPURM, OND, CDER
FDA United States
Our study sought to evaluate FDA’s pregnancy and lactation Post Marketing Requirements (PMRs), from the introduction of the FDA Amendments Act (FDAAA) in 2007 to 2020, and to identify past and present trends.
Pregnancy and Lactation PMRs and original NDA/BLA approvals from 2007-2020 were identified from internal FDA databases. PMRs were verified using the approval letter within the Drugs@FDA database. The data were analyzed for trends in the number and type of PMRs issued across therapeutic areas.
We identified 488 original NDA/BLA approvals from 2007-2020. Of the total number of approvals, 95% (462) were drugs that may be used in females of reproductive potential (FRP). Of those that may be used in FRP, 18% (85) were issued a pregnancy or lactation PMR. The most common drugs to receive a pregnancy PMR (n=71) were for migraine (n=6, 9%), plaque psoriasis (n=7, 10%), and multiple sclerosis (n=6, 9%). The most common drugs to receive a lactation PMR (n=14) were for sleep disorders (insomnia and narcolepsy) (n=4, 29%), and chronic idiopathic constipation (n=4, 29%). Since the passage of FDAAA, there has been a 13-fold increase in pregnancy PMRs and a 7-fold increase in lactation PMRs. Prior to 2014, there was an average of 3 pregnancy PMRs per year with an increase to 12 in 2014.The largest increase in both pregnancy and lactation PMRs occurred from 2016 to 2019 (3 to 29 and 0 to 7, respectively). After 2016, there was also an increase in the number of products that were issued more than one pregnancy PMR (i.e., both a pregnancy registry study and a complementary claims database study) with 1 in 2016, 5 in 2017, 4 in 2018, 10 in 2019, and 7 in 2020.
Because safety data in pregnant and lactating women are generally collected post approval, PMRs are an important regulatory mechanism to obtain safety data in pregnant and lactating women. Since the passage of FDAAA in 2007, there has been an increase in pregnancy and lactation PMRs. However, our analysis shows that only 18% of products that could be used in females of reproductive potential were required to conduct pregnancy and/or lactation studies post-approval. The paucity of pregnancy and lactation PMRs reflects the historical underrepresentation of pregnant and lactating women in research. However, there appears to be an increase in the number of PMRs issued over the last six years. This trend may be related to an increased awareness of the need for these types of studies because of FDA guidances, workshops, and public meetings since 2014. A limitation of this analysis includes that products such as vaccines approved in the Center for Biologics Evaluation and Research were not evaluated and do not reflect all the pregnancy PMRs that were issued. Future analyses to address this limitation would be helpful. There is a need for more comprehensive data collection in pregnant and lactating women, as articulated in FDA guidance. In May 2019, FDA published the draft “Postapproval Pregnancy Safety Studies Guidance for Industry” which describes general approaches to evaluate product safety during pregnancy and the draft “Clinical Lactation studies: Considerations for Study Design, Draft Guidance for Industry” which describes when and how to conduct lactation studies. Future reviews will hopefully demonstrate improvements in stakeholder’s recognition of the importance of collecting data in pregnant and lactating women in order to address gaps in knowledge on the safety of medication use in this population.