Pharmacogenetic Labeling of FDA-Approved Drugs: A Regulatory Retrospective

Abstract

The U.S. Food and Drug Administration recently marked 10 years since first updating the labeling for warfarin (often referred to as the "poster child" of pharmacogenomics) to include information regarding the potential impact of CYP2C9 and VKORC1 genetic variation on warfarin dosing requirements and risks. Herein, we opine on the experience updating the warfarin labeling, highlighting more generally the enabling factors and challenges encountered when considering incorporation of pharmacogenomic information into the prescribing recommendations for already approved drugs. We also provide a historical perspective of implemented changes in regulatory policies related to personalized medicine.

Keywords: drug labeling; pharmacogenomics; precision medicine; regulatory perspective; warfarin.

Graphical abstract

Figure 1

Novel Drugs Approved (NME/BLA) Between 2007 and 2017 With Genomic and Other Selected Biomarker Information in Labeling Shaded areas depict oncology drugs. Actionable biomarker information refers to a specific prescribing recommendation that is included in one of the following label sections: 1) Boxed Warning, 2) Indications and Usage, 3) Dosage and Administration, 4) Contraindications, or 5) Warnings and Precautions. Biomarkers may be any genomic biomarker or other selected protein biomarker that are used for patient selection. BLA = Biologic License Application; NME = New Molecular Entity.

Figure 2

Timeline of Regulatory Guidances and Policies Related to Precision Medicine ∗Draft. ICH = The International Council for Harmonization; IVD = In vitro diagnostic; NGS = Next-generation sequencing; PDUFA = Prescription Drug User Fee Act.