Guidance Snapshots are a communication tool and are not a substitute for the guidance document.

To learn more about population PK, read the final guidance:

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/population-pharmacokinetics

What is Recommended in this Guidance?

The final guidance entitled "Population Pharmacokinetics" describes the application of

population PK in drug development and its role in informing therapeutic individualization.

This guidance provides the FDA’s current thinking on the data and model submissions to 

support regulatory decisions and recommendations on how to incorporate information from

population PK analyses in labeling. The guidance also lays out the general expectations

regarding the format and content for population PK reports submitted to the Agency.

What is Population PK?

Population PK integrates all relevant PK information to identify factors that can affect a

drug’s exposure in an individual. A population PK analysis can be used to guide drug 

development and inform recommendations on therapeutic individualization (e.g., through

tailored dosing).

Population PK Goal: Minimize Treatment Response Variability by Informing 

Dosing and Administration for Individuals or Subpopulations

Treatment

Population

PK Analysis

Subpopulations

AUC

Tailored

Dose

AUC = area under the curve

Dr

ug Con

centratio

n

Time

Population Pharmacokinetics 

Final Guidance

www.fda.gov
What are Potential Applications for Population PK?

• Selecting Dosing Regimens To Be Tested in Clinical Trials

• Informing Trial Design to Facilitate the Reliable Estimation of Covariate Effects

• Deriving Exposure Metrics for Conducting Exposure-Response Analysis

• Informing Pediatric Study Designs

• Selecting Dosing for Specific Populations

How are Population PK Results Presented in the Labeling?

Results from population PK analysis may be presented in the CLINICAL PHARMACOLGY 

section and summarized in other sections of labeling, as appropriate, but the results don’t 

need to explicitly state that the information is based on population PK analysis. Labeling 

recommendations are provided in the FDA guidance for industry entitled Clinical 

Pharmacology Section of Labeling for Human Prescription Drug and Biological Products - 

Content and Format. 

Sponsors should perform 

preliminary examination of the 

data using graphical and statistical 

techniques to reveal patterns and 

features in the population dataset.

When models are used for simulations, 

these models should be evaluated to 

address the specific question the 

simulation is trying to answer. 

Depending on the purpose of the model, 

various levels of uncertainty and 

variability should be incorporated into 

the simulations. Examples for evaluating 

various types of simulations are 

provided in the Population PK final 

guidance.

4. Simulations

Based on 

Population

PK Models

1. Preliminary

Examination

of the Data

Model validation should be conducted to 

examine whether the developed 

model can sufficiently characterize the 

observed data to meet the needs of the 

analysis with an acceptable level of bias and 

an acceptable degree of precision. Basic 

goodness-of-fit (GOF) plots can illustrate 

how well the model describes the observed 

data. In general, several methods should be 

considered to adequately assess model 

performance and follow a fit-for-purpose 

approach. 

3. Model 

Validation

Model development methods and best 

practice recommendations are

 constantly evolving. Sponsors should 

explicitly describe their model 

development procedures; some aspects 

include covariate identification, choice 

of the structural model, and 

distinguishing between outlying 

individuals and outlier data points. 

2. Model

Development

To learn more about population PK, read the final guidance:

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/population-pharmacokinetics

Analysis of Population PK Data

www.fda.gov

Guidance Snapshots are a communication tool and are not a substitute for the guidance document.
Why is This Guidance Important?

Drug Development Timeline 

Apply Guidance Recommendations During and After Clinical Development

Seek Advice Prior to and During Clinical Studies

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. Confidence 

in a given population PK analysis is increased by the following: 

Guidance Recap Podcast

Basic

Research

Prototype Design

or Discovery Preclinical

Development Phase 1 Phase 2 Phase 3

Clinical Development

Basic 

Research

Prototype Design

or Discovery

Preclinical

Development

FDA Filing 

Approval

Post-Market/

Post-Approval

Studies

Phase 1 Phase 2 Phase 3

Hear Highlights Straight From FDA Staff

Speaker: Hao Zhu, Ph.D., Acting Director of the Division of Pharmacometrics in 

the Center for Drug Evaluation and Research’s Office of Clinical Pharmacology 

• Understanding of the drug’s PK properties

• Prespecified questions in the study protocol or

analysis plan that will be addressed by a population 

PK analysis 

• Sufficient PK data that represents the indicated

population and relevant subpopulations of interest 

• Good model performance (i.e., the model should

describe the data with acceptable bias and precision) 

and valid for the intended purpose 

Click here to Listen Click here to read Transcript

To learn more about population PK, read the final guidance.

To see additional Guidance Snapshots, check out the pilot program.

www.fda.gov

The population PK guidance includes common 

applications of population PK analyses to inform drug 

development and drug use. The guidance also provides 

FDA’s current thinking on the population PK data and 

model submissions to support regulatory decisions, 

how to incorporate population PK analyses in the 

labeling, and the general expectations regarding the 

format and content for population PK reports submitted 

to the Agency. Population PK models are of great utility 

in dose optimization as they can be used to simulate 

drug exposures that are expected to occur following 

doses or dosing regimens that have not been directly 

investigated in prior clinical studies. This guidance is 

timely and relevant, as it supports FDA’s efforts and 

focus on model-informed drug development and the 

application of quantitative models for regulatory 

decision-making, including those derived through 

population PK approaches.

Guidance Snapshots are a communication tool and are not a substitute for the guidance document.