FDA Revises 1999 Draft Guidance on Population Pharmacokinetics
The US Food and Drug Administration (FDA) on Thursday released revised draft guidance to help keep sponsors informed on the data and model requirements for population pharmacokinetics (PK) analyses submitted as part of new drug applications and biologic license applications.Since the original population PK guidance was published in 1999, FDA says the number of applications relevant for population PK analysis has increased and, “The sophistication and reliability of population PK analysis methods have improved.”
Specifically, the revised, 23-page draft guidance includes a description of the types of scientific and regulatory questions appropriate for population PK analysis and outlines FDA's recommendations for data analysis and modeling. Recommendations on the format and content of population PK reports submitted to FDA as well as any labeling statements informed by the results of these analyses are also included.
“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 healthy volunteers,” the draft says. “In addition, the relatively large numbers of patients included in population PK analysis may improve the precision of the estimated effect of the factors that affect drug exposures and confirm which factors do not change drug exposures.”
The draft addresses the application of population PK analysis in drug development and to inform drug use, with further discussions on selecting dosing regimens to be tested in clinical trials, deriving exposure metrics for conducting exposure-response analysis, pediatric study designs and drug-drug interactions, among other sections.
The section on data analysis also provides further help on the methodological aspects of population PK analysis and includes a discussion of simulations based on population PK models, which touches on fixed-effect estimates and estimates of between-subject variability.
At the end of the draft, FDA also includes a table explaining the expected content in each section of the population PK study report.
Population Pharmacokinetics: Draft Guidance for Industry