Characterizing interactions between new molecular entities (NMEs) and drug transporters is a critical element of drug development that helps in assessing potential transporter-based drug–drug interactions (DDIs). However, not all NME new drug applications (NDAs) include a full characterization of NMEs transporter-based DDIs, which necessitates the issuance of post-marketing requirement (PMR)/post-marketing commitment (PMC) by the US Food and Drug Administration (FDA) to characterize these potential interactions. The objective of this analysis is to identify trends in transporter-based PMRs/PMCs issued by the FDA between 2012 and 2021. A decrease in the number of transporter-based PMRs/PMCs was observed from 2012 to 2016 and an increasing trend in the number of PMRs/PMCs was observed after 2017. The majority of these transporter-based PMRs/PMCs requested clinical evaluation (48%), some requested in vitro assessment (38%), and 2.5% requested modeling and simulation assessment. Most of the PMRs/PMCs requested evaluation of NMEs as perpetrator with the efflux transporters, P-gp and/or BCRP (53%). Forty-eight percent of the PMRs/PMCs were fulfilled with 67% resulted in labeling updates. On average, 2.5 years were needed for the information related to PMRs/PMCs to show in NMEs labeling. In conclusion, this analysis highlights the increased emphasis from the FDA on proper characterization of transporter-based DDI and call for the need of early characterization of NMEs-transporters interaction before initial NDA approval.

中文翻译：

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过去十年基于 FDA 转运蛋白的上市后要求和承诺的趋势

表征新分子实体 (NME) 和药物转运蛋白之间的相互作用是药物开发的关键要素，有助于评估潜在的基于转运蛋白的药物-药物相互作用 (DDI)。然而，并非所有 NME 新药申请 (NDA) 都包含基于 NME 转运蛋白的 DDI 的完整表征，这需要美国食品和药物管理局发布上市后要求 (PMR)/上市后承诺 (PMC)。 FDA）来描述这些潜在的相互作用。本分析的目的是确定 FDA 在 2012 年至 2021 年期间发布的基于转运蛋白的 PMR/PMC 的趋势。从 2012 年到 2016 年，基于转运蛋白的 PMR/PMC 的数量有所减少，并且数量呈上升趋势在 2017 年之后观察到 PMRs/PMCs 的数量。体外评估（38%），2.5% 要求建模和模拟评估。大多数 PMR/PMC 要求评估 NME 作为外排转运蛋白、P-gp 和/或 BCRP 的肇事者（53%）。48% 的 PMR/PMC 得到满足，其中 67% 导致标签更新。与 PMRs/PMCs 相关的信息平均需要 2.5 年才能显示在 NMEs 标签中。总之，该分析强调 FDA 越来越重视基于转运蛋白的 DDI 的适当表征，并呼吁在初始 NDA 批准之前对 NMEs-转运蛋白相互作用进行早期表征。