(235) Analysis of Postapproval Pregnancy Safety Studies Associated with FDA Approved Products

Background: Pregnant individuals are often excluded from clinical trials (RCTs); therefore, postapproval pregnancy safety studies are important to gather additional information about products’ safety after approval. Under section 505(o)(3) of the Food, Drug, and Cosmetic Act (FDCA), postapproval safety studies can be required by FDA to assess known and unexpected serious risk related to the use of a drug.

Objectives: As part of the Prescription Drug User Fee Act (PDUFA) VII commitment, FDA was charged with developing a postapproval pregnancy safety study framework. To support framework development, this study was undertaken to understand the impact of different types of postapproval pregnancy safety studies on changes to prescription product labeling.

Methods: This is a cross-sectional descriptive analysis using three data sources; (1) FDA postapproval pregnancy safety database, (2) FDA’s Office of Women’s Health Pregnancy Registry website, and (3) ClinicalTrials.gov. We identified pregnancy safety studies issued or initiated by May 31, 2022 to monitor maternal, fetal, and infant outcomes associated with exposure to FDA approved drugs, vaccines, or biological products. We collected information on study type, therapeutic area, study status, and any resultant labeling updates.

Results: We identified 333 studies representing 270 products (230 drugs and 40 biologics); 209 studies (63%) were pregnancy exposure registries, 69 (21%) were descriptive pregnancy safety studies, 52 (15%) were database studies, and 3 (1%) were RCTs. The most common therapeutic areas were Psychiatry (21%), Neurology (18%), Prophylactic Vaccines and Related Biologics (14%), Dermatology (8%), Metabolic (7%), Reproductive (5%), Genetic (5%), and Rheumatology (4%). Majority of the studies were established in the last 10 years. As of July 2023, 230 studies (69%) were ongoing, 65 studies (20%) were completed, and 38 studies (11%) were released or terminated. Majority of the terminated studies were deemed infeasible due to low enrollment. Forty-eight percent of completed studies resulted in a pregnancy safety labeling update with an average time of 11 years (range 6 – 18 years) from study issuance to labeling update.

Conclusions: Only a small proportion of postapproval pregnancy safety studies have been completed; of those, less than half resulted in any revisions to product labeling. The low proportion of completed studies may be due to most studies being implemented in the past 10 years, and the many years required to complete pregnancy safety studies due to low product utilization in pregnancy. This data will be used to inform the design of the PDUFA VII pregnancy safety framework to optimize post-approval pregnancy safety data collection.