Trends in FDA Transporter-Based Post-Marketing Requirements and Commitments Over the Last Decade

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Drug Development and Regulatory Science

Background:

• Characterizing drug transporter interactions is crucial for identifying potential drug-drug interactions (DDIs).
• US Food and Drug Administration (FDA) often issues post-marketing requirements (PMRs)/post-marketing commitments (PMCs) for new molecular entities (NMEs) lacking transporter DDI data.

Purpose of the Study:

• To analyze trends in transporter-based PMRs/PMCs issued by the FDA between 2012 and 2021.
• To understand the types of assessments requested and the outcomes of these regulatory actions.

Main Methods:

• Retrospective analysis of FDA PMRs/PMCs related to drug transporter interactions from 2012 to 2021.
• Categorization of requested assessments (clinical, in vitro, modeling) and targeted transporters (e.g., P-gp, BCRP).

Main Results:

• A decrease in PMRs/PMCs was observed from 2012-2016, followed by an increasing trend after 2017.
• Clinical evaluations were most frequently requested (48%), followed by in vitro assessments (38%).
• Most PMRs/PMCs focused on NMEs as perpetrators involving efflux transporters (P-gp/BCRP) (53%); 48% were fulfilled, leading to labeling updates in 67% of cases.

Conclusions:

• The FDA shows an increasing emphasis on characterizing transporter-based DDIs.
• Early characterization of NME-transporter interactions before initial New Drug Application (NDA) approval is recommended.