FDA Announces Availability of a Revised Draft Guidance, Pharmacokinetics in Patients with Impaired Renal Function -- Study Design, Data Analysis, and Impact on Dosing

FDA Announces Availability of a Revised Draft Guidance, Pharmacokinetics in Patients with Impaired Renal Function -- Study Design, Data Analysis, and Impact on Dosing

On September 4, 2020, the U.S. Food and Drug Administration (FDA) announced the availability of a revised draft guidance for industry titled “Pharmacokinetics in Patients with Impaired Renal Function -- Study Design, Data Analysis, and Impact on Dosing.” This revised draft guidance assists sponsors in the design and analysis of studies that assess the influence of impaired renal function on the pharmacokinetics and/or pharmacodynamics of an investigational drug and addresses how such information can inform product labeling.

Drugs are eliminated from the body by a variety of mechanisms, including renal excretion. If a drug is eliminated primarily through renal excretion, then impaired renal function usually alters the drug’s pharmacokinetics to an extent that a change in the dosing regimen from that used in patients with normal renal function should be considered. However, individuals with advanced renal disease are frequently excluded from participation in late-phase clinical trials, hindering the determination of a safe and effective dosing regimen for this patient population. A well-planned drug development program can enable prospective dosage adjustment based on the observed or expected changes in the pharmacokinetics of a drug due to impaired renal function prior to initiating phase 2 or phase 3 trials.

This guidance revises and replaces the draft guidance titled “Pharmacokinetics in Patients With Impaired Renal Function --Study Design, Data Analysis, and Impact on Dosing and Labeling” (March 2010). It provides updated recommendations on: (1) when a standalone study of a drug’s pharmacokinetics in subjects with impaired renal function is recommended; (2) the design and conduct of pharmacokinetic studies in subjects with renal impairment; (3) considerations for characterizing a drug’s pharmacokinetics in patients undergoing intermittent or continuous dialytic therapies; (4) the use of pharmacokinetic information from phase 2 and 3 studies to inform dosing recommendations for patients with renal impairment; and (5) the analysis and reporting of results from studies that characterize the impact of renal impairment and how these data inform dosing.

The “Pharmacokinetics in Patients With Impaired Renal Function -- Study Design, Data Analysis, and Impact on Dosing” guidance is available at https://go.usa.gov/xGThK. Please refer to the revised draft guidance for more details. FDA is publishing this revised draft guidance to collect additional public comments. You may submit your comments regarding the draft guidance to the docket (Docket No. FDA-2010-D-0133) available at https://www.regulations.gov up to 90 days following publication in the FEDERAL REGISTER. This revised draft guidance, when finalized, will represent the current thinking of the FDA on this topic. It does not establish any rights for any person and is not binding on FDA or the public. Your comments do make a difference and can impact the outcomes of FDA regulatory policy. Share your knowledge and experience and make your voice count.

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