2023 FDA Science Forum
Regulatory Impact of Post Marketing Safety Registries Submitted to FDA to Fulfill a Post Marketing Safety Requirement
- Authors:
- Center:
-
Contributing OfficeCenter for Drug Evaluation and Research
Abstract
Background
One of the U.S. Food and Drug Administration (FDA)’s missions is to ensure that drugs already marketed remain safe for as long as the drugs remain on the U.S. market.
FDA uses several postmarketing surveillance tools for drug product safety signal detection including Postmarketing Requirements (PMRs) and Postmarketing Commitments (PMCs).
The main goals of requesting PMR and PMC safety studies are to assess the known and unknown risks, or adverse events, associated with the real-world use of the drug product. The evaluation of final study reports helps the FDA to make regulatory decisions such as updating the labeling to inform providers and patients about potential risks associated with the product use.
Purpose
To assess the regulatory impact of long-term postmarketing safety studies on drug product labeling update.
Methodology
Postmarketing safety studies were identified in internal record repositories for the Center for Drug Evaluation and Research (CDER). The assessment included long-term (at least 2 years) postmarketing safety registries conducted for drug products used to treat inflammatory or autoimmune conditions, approved by Divisions of Dermatology, Rheumatology, and Gastroenterology.
Results
This paper analyzed 10 safety (non-pregnancy) registries and 4 pregnancy registries (n=14). Most of these registries (5 safety registries and 4 pregnancy registries) addressed the safety of Tumor Necrosis Factor Alpha (TNF-α) inhibitors, and malignancies were the most common (8 studies) safety outcomes of interest in safety registries. Four of the 8 safety registries with pre-specified enrollment targets and 2 of the 4 pregnancy registries did not reach their pre-specified enrollment targets. Ten registries lasted for at least 5 years, but only 4 (safety) registries reached their targets for person-years (PYs) of follow-up time. While all 4 pregnancy registries resulted in labeling update, none of the 10 safety registries had a regulatory impact in terms of safety labeling update due to various study limitations. However, these safety registries were successful in producing final study reports that fulfilled their PMR or PMC requirements.
Conclusions
Safety registries may not be the best tool to evaluate post marketing drug safety especially with respect to adverse events with long latency, such as malignancies.
