P202: Characterization of Newly Identified Safety Signals for Marketed Drugs by the US Food and Drug Administration, 2020-2024
Poster Presenter
Maryann Rose Chapin
ORISE Fellow
Food and Drug Administration United States
Objectives
To better understand the characteristics of Newly Identified Safety Signals (NISS) opened in FDA’s Center for Drug Evaluation and Research (CDER) since the implementation of the Manual of Policies and Procedures for the collaborative identification, evaluation, and resolution of NISS in 2020.
Method
We retrospectively analyzed NISS opened for marketed drugs between April 27, 2020, and April 26, 2024, and closed as of May 1, 2024. We extracted data from FDA’s internal repositories and characterized each NISS by drug attributes, adverse events, data sources, outcomes, and administrative details.
Results
We identified 820 NISS opened during our study window whose status was “closed.” Seventy-four percent of NISS involved drug products, 24% concerned therapeutic biologics, and 4% involved other products including homeopathic and unapproved products. A small number of NISS (0.7%), evaluated both drug and therapeutic biologics. Most NISS (78%) focused on a single active ingredient, whereas the remainder expanded to drug combinations (14%; e.g., products involved in drug-drug interactions) or pharmacological drug classes (8%). Safety issues were coded with Medical Dictionary for Regulatory Activities (MedDRA) terminology. The top recorded System Organ Classes (SOCs) were Immune system disorders (11%; e.g., hypersensitivity, anaphylactic reaction); Injury, poisoning and procedural complications (9%; e.g., wrong drug, wrong dose); and Gastrointestinal disorders (7%; e.g., pancreatitis, colitis). The majority of NISS were identified from postmarketing reports in the FDA Adverse Event Reporting System (FAERS) (52%), medical literature (26%), and periodic safety reports from drug manufacturers (8%). NISS evaluations commonly involved multiple data sources, with FAERS (88%), medical literature (71%), and periodic safety reports (41%) being used most frequently. FDA also utilized other data sources for NISS evaluations such as the America’s Poison Centers National Poison Data System (NPDS), clinical trial data, drug utilization data, observational studies, and non-clinical data. Regulatory action resulted from 190 (23%) NISS, with product labeling updates being most common (82%), followed by public communications (14%). The most frequently updated labeling sections included Warnings and Precautions, Adverse Reactions, and Patient Counseling Information. Additional forms of public communications included Drug Safety Communications, consumer updates, and drug recall notifications.
Conclusion
CDER manages a high volume of diverse safety signals across a wide range of drug product types, including both approved and unapproved products, drugs and biologic products, and single entities or drug classes. The safety issues that are the focus of the NISS span different categories (e.g., adverse events, medication errors) and organ systems often representing clinically serious conditions, such as hypersensitivity and pancreatitis. Signals originate from a variety of different data sources, with FAERS being the most common source of postmarketing safety signal data, underscoring the importance of FDA’s MedWatch program and FDA’s drug safety surveillance program. Although FAERS data remains the cornerstone for both signal identification and evaluation, FDA reviews the totality of data and integrates data from various data sources to evaluate signals. Not all FDA signal assessments result in action, but the NISS process frequently leads to the implementation of measures aimed at improving patient safety. The actions are often conveyed in the form of labeling, FDA’s primary tool for communicating safety information to healthcare professionals and patients. FDA implemented the NISS Manual of Policies and Procedures in 2020 to provide a high-level overview for the signal management process, encompassing signal identification, evaluation, and regulatory action when necessary. This comprehensive characterization of NISS enhances understanding of the scope of safety issues assessed by the FDA and informs potential future directions to strengthen signal management.
