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  5. Model | Data Format
  1. Center for Drug Evaluation and Research (CDER)

Model | Data Format

The following are the general expectations for submitting pharmacometric data and models: 

  • The Specification for File Format Types Using eCTD Specifications document1 provides a listing of many file formats, file types, and file locations that can be used in population pharmacokinetic, physiologically based pharmacokinetic, exposure-response, and other pharmacometric analyses for eCTD submissions.
  • If a file format planned for submission is not listed in this document, the sponsor can discuss how to submit datasets and codes with the review team.
  • Pharmacometric analysis reports for new drug applications (NDAs) and biologic license applications (BLAs) can be submitted in Module 5.3.3.5.
  • All datasets used for model development, validation, and simulations can be submitted as SAS transport (*.xpt) or comma delimited (*.csv) files.1
  • A description of each dataset and associated variables can be provided in a define file (as an *.xml or *.pdf).
  • A Reviewer’s Guide file can also be provided and includes the following information:
    1. Listing and description of all submitted analysis scripts, software, version, and package dependencies needed to run the analysis scripts
    2. Specific order for execution 
    3. Flowchart and/or table depicting input and output files for each analysis script
       
  • Model codes or control streams and output listings can be provided for all major model building steps (e.g., base structural model, covariates models, final model, validation model).
     
  • Files for generating key tables and figures in the report and relevant simulations can also be included. These files can be submitted as ASCII text files. It is not necessary to rename ASCII files ending in different extensions (e.g., .R, .sas, .ctl) to a file with a *.txt extension for submission.1 In addition, project files (e.g., .rmd, .phxproj) can also be included with a submission.
     
  • For population pharmacokinetic and exposure-response analysis reports, we request the following:
     
    1. In addition to the standard model diagnostic plots, submit individual plots for a representative number of subjects. Each individual plot should include observed concentrations, the individual prediction line, and the population prediction line.
       
    2. In the report, tables should include model parameter names and units. For example, oral clearance should be presented as CL/F (L/h) and not as THETA(1).
       
    3. Reports should include a summary of the clinical application of the modeling results, including how analysis results are being used to support labeling claims and
      dosing within the submission. 
       
    4. Covariate assessments should include a description of how the covariate alters exposure parameters (e.g., AUC, Ctrough) or response rates, not just the impact of the covariates on the model parameter. 

References:

  1. The Specification for File Format Types Using eCTD Specifications can be found in the eCTD Submission Standards on the FDA eCTD webpage: https://www.fda.gov/drugs/electronic-regulatory-submission-and-review/electronic-common-technical-document-ectd
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