FDA Releases Updated Draft Guidance on Population PK

July 16, 2019
The Center for Biosimilars Staff

The FDA has released updated draft guidance on population pharmacokinetics (PK). The update follows draft guidance originally put forth by the agency in 1999.

The FDA has released updated draft guidance on population pharmacokinetics (PK). The update follows draft guidance originally put forth by the agency in 1999.

The guidance aims to assist developers submitting New Drug Applications and Biologics License Applications (BLAs) with applying population PK analysis, which quantifies and explains the variability in drug concentrations among individuals and can sometimes reduce the need for postmarketing requirements or commitments.

Because stand-alone studies are usually designed to focus on intrinsic and extrinsic factors that have a high potential to affect drug exposure, they leave other possible interactions unstudied; population PK analysis allows for an assessment of multiple factors that are not otherwise evaluated in healthy volunteers and allows for a large number of patients to be included.

According the updated draft guidance, sponsors are encouraged to use all available data to support their population PK models; data sets should include a sufficient number of subjects with adequate PK samples at informative timepoints, and sponsors should be aware that, as the number of samples per subject decreases, the importance of the timing of PK sampling increases. Sponsors are encouraged to collect PK data from all included patients.

The guidance also provides a description of methodological aspects of population PK analysis, including examination of the observed data, model development, model validation, and simulations based on population PK models. It also outlines the recommended content and format for a drug sponsor to submit its population PK analysis in support of its clinical pharmacology program.

Population PK is becoming an increasingly important way for drug sponsors to provide information about the impact of multiple factors on the PK of their products; one recent study reported that biologics whose data included population PK models most frequently included body size as a covariate in final models, although age, sex, race, and renal function are also included in some models. In 70% to 90% of cases in which these covariates are examined, information from the population PK studies is eventually included in product labels.1

According to another recent paper, population PK modeling and simulation analysis is almost always a component of BLAs for novel drugs, and these analyses can provide a robust knowledge base to support biosimilar development, as they can help with optimizing study design.2


1. Ogasawara K, Alexander GC. Use of population pharmacokinetic analyses among FDA-approved biologics [published online February 1, 2019]. Clin Pharamcol Drug Dev. doi: 10.1002/cpdd.658.

2. Wang YC, Wang Y, Schrieber SJ, et al. Role of modeling and simulation in the development of novel and biosimilar therapeutic proteins. J Pharm Sci. 2019;108(1):73-77. doi: 10.1016/j.xphs.2018.10.053.