Developing a Prediction Model to Estimate the Magnitude of Exposure

On September 30, 2022, the President signed into law the FDA User Fee Reauthorization Act of 2022. This law included the sixth reauthorization of the Prescription Drug User Fee Act (PDUFA VII) and provided FDA with the necessary resources to maintain a predictable and efficient review process for human drug and biologic products. FDA committed to the “Enhancement and modernization of the FDA drug safety system.” The enhancement and modernization include an effort to optimize the Sentinel Initiative and describe a focus on supporting FDA’s monitoring of medical product safety during pregnancy.

As part of these enhancements, FDA has developed a framework addressing how to optimize use of post-approval pregnancy safety studies. To support the development and use of this framework, the Sentinel System will develop a quantitative model to estimate the magnitude of drug exposure during pregnancy. This model will incorporate directly measured characteristics (such as prevalence of indication) as well as coded qualitative characteristics (such as whether a drug is first-in-class or designated a breakthrough therapy), weighted by solving a regression model for an assembled “ground truth” data set. For a given drug, the model will output an estimated category of magnitude of potential exposure for that drug. This estimated category will help inform decisions regarding post-market pregnancy safety assessments requested or required by FDA, including whether such assessments are likely to be feasible using pregnancy registries and/or electronic healthcare database studies.