FDA Announces Availability of the Draft Guidance “Population Pharmacokinetics”

On July 11, 2019, the U.S. Food and Drug Administration (FDA) announced the availability of a draft guidance for industry entitled "Population Pharmacokinetics."

Population pharmacokinetic (population PK) analysis is frequently used to guide drug development and inform recommendations on therapeutic individualization (e.g., through tailored dosing). Adequate population PK data collection and analyses submitted in marketing applications have in some cases alleviated the need for postmarketing requirements (PMRs) or postmarketing commitments (PMCs). This guidance is intended to assist sponsors of new drug applications (NDAs) and biologics license applications (BLAs) in the application of population PK analysis.

Population PK analysis is a well-established, quantitative method that can quantify and explain the variability in drug concentrations among individuals. Drug concentrations can vary significantly among individuals who are following the same dosing regimen. Variability can be attributed to intrinsic patient factors, such as the presence and extent of liver or renal impairment or the presence of genetic polymorphisms, or to extrinsic patient factors, such as food consumption or concomitant medications that may interact with the administered drug. In some cases, intrinsic or extrinsic factors lead to clinically relevant changes in drug concentrations that require clinical management strategies, such as a change in the dose or dosing regimen. Population PK analysis typically includes data directly collected from patients, allowing an assessment of multiple intrinsic and extrinsic factors that are not otherwise evaluated in stand-alone clinical pharmacology studies in healthy volunteers. In addition, the relatively large numbers of patients included in population PK analyses may improve the precision of the estimated effect of the factors that affect drug exposures and confirm which factors do not change drug exposures.

This guidance includes common applications of population PK analysis to inform drug development and drug use. This guidance also includes the FDA’s current thinking on the data and model requirements needed to support regulatory decisions, recommendations to sponsors on drug labeling based on population PK analysis, and the general expectations regarding the format and content for population PK reports submitted to the Agency. Sponsors seeking advice on the use of population PK analysis for drug development decisions or to answer regulatory questions are encouraged to do so at appropriate milestone meetings with the Agency. Sponsors should contact the Office of Clinical Pharmacology to discuss novel methodologies and applications of population PK analyses to inform drug development and use.

The "Population Pharmacokinetics" draft guidance is available at https://go.usa.gov/xyNPT. Please refer to the draft guidance for more details. FDA is publishing this draft guidance to collect additional public comments. You may submit your comments regarding the draft guidance to the docket (Docket No. 2019-14856) available at https://www.regulations.gov up to 60 days following publication in the FEDERAL REGISTER. This 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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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.