Clinical pharmacology information in regulatory submissions and labeling: A comparative analysis of orphan and non‐orphan drugs approved by the FDA

Abstract

Clinical pharmacology is an integral discipline supporting the development, regulatory evaluation, and clinical use of drugs for the treatment of both common and rare diseases. Here, we evaluated the recommendations and information available from select clinical pharmacology studies in the therapeutic product labeling of new molecular entities (NMEs) approved from 2017 to 2019 for both common and rare diseases. A total of 151 NMEs, including 72 orphan and 79 non-orphan drugs, were analyzed for recommendations and information available related to fooddrug interaction, drug-drug interaction, renal impairment, hepatic impairment, QT assessment, and human radiolabeled mass balance studies using data collected from the original labeling and other regulatory documents. The analysis showed no statistically significant difference in the recommendations between orphan and non-orphan drugs except for renal impairment related recommendations in section 8 of the labeling. Although not significant, fewer hepatic impairment labeling recommendations were available for orphan drugs when compared with non-orphan drugs. At the time of initial approval, 79 postmarketing requirements (PMRs) and postmarketing commitments (PMCs) for 33 orphan drugs and 39 PMRs and PMCs for 19 non-orphan drugs were established; with most difference observed for drugdrug interaction, hepatic impairment, and QT assessment. Overall, although there was a trend for more labeling recommendations and fewer postmarketing studies and clinical trials for non-orphan drugs, there appeared to be no substantial differences in how these select clinical pharmacology studies are leveraged during the development and approval of orphan and non-orphan drugs. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?As a discipline, clinical pharmacology can be leveraged to support development, regulatory evaluation, and clinical use of drugs for common and rare diseases.

US FDA Postmarketing Requirements and Commitments: A Systematic Assessment of Clinical Pharmacology Studies and Their Impact on US FDA Prescribing Information

“…Previous research has evaluated PMRs and PMCs relevant to clinical pharmacology in narrowly focused topic areas 3–6 . Here, we conducted a comprehensive evaluation of clinical pharmacology–related PMRs and PMCs established at the time of initial NME approval between 2009 and 2020.…”

“…Previous research has evaluated PMRs and PMCs relevant to clinical pharmacology in narrowly focused topic areas. [3][4][5][6] Here, we conducted a comprehensive evaluation of clinical pharmacology-related PMRs and PMCs established at the time of initial NME approval between 2009 and 2020. We characterized the PMRs and PMCs, the disposition of these studies over time, and the impact of fulfilled PMRs and PMCs on PI.…”