Risk for Postmarket Black Box Warnings in FDA-Approved Monoclonal Antibodies

Abstract

Objective: To estimate the potential risk for a future postmarket black box warning (BBW) of US Food and Drug Administration (FDA)-approved monoclonal antibodies (mAbs) because of the importance for medical clinicians to understand mAb risks and benefits, including unknown future risks, especially for recently approved mAbs. Methods: The complete dates of the study were March 16, 2020, through May 12, 2021. We searched the FDALabel database online and reviewed the scientific literature to determine current and previous FDAapproved mAbs as of March 2020. The BBWs and initial FDA-issued safety warnings were identified. The BBWs were categorized as premarket or postmarket. For mAbs with specific postmarket BBWs, previous FDA labels were evaluated to identify the presence or absence of an initial corresponding specific FDA warning. Results: In March 2020, a total of 83 mAbs had FDA approval; 33 had BBWs (27 premarket and 13 postmarket BBWs). Of these 33 mAbs, 55 individual specific BBWs existed (36 premarket and 19 postmarket specific warnings). On average, the specific BBWs occurred in the postmarket period at a rate of 3.4% (19/562) per year. Most (73.7%; 14/19) specific postmarket BBWs were preceded by an FDA warning in a median time of 3.61 (interquartile range, 1.36-5.78) years. Specific postmarket BBWs not preceded by a specific FDA product label warning occurred at an average rate of 0.9% (5/562) per year. Conclusion: Specific postmarket BBWs occurred in FDA-approved mAbs at a rate of 3.4% per year. Specific postmarket BBWs not preceded by a specific FDA product label warning had a rate of 0.9% per year.

Nationwide Laboratory Surveillance of Progressive Multifocal Leukoencephalopathy in Japan: Fiscal Years 2011–2020

“…However, in most cases, reporting the occurrence of PML to the government is not mandatory, except for drug-safety monitoring purposes. Despite comprehensive studies on PML with possible adverse events caused by pharmaceutical products [28][29][30][31][32][33][34][35][36][37][38][39], gathering comprehensive information on each PML case across Japan has been challenging. Historically, several strategies have been employed to identify and analyze non-reportable PML cases, including single-center chart reviews of empirical cases [40][41][42][43][44], multicenter observational studies of patients primarily with targeted clinical conditions [25,[45][46][47][48][49][50], estimates based on searches of large-scale public databases containing relevant information [51][52][53][54][55][56][57][58], and literature or systematic reviews of individual case reports in related fields [43,47,[59][60][61][62][63][64][65][66][67]…”