On September 4, 2018, the FDA issued final guidance on Physiologically Based Pharmacokinetic Analyses — Format and Content.  The guidance outlines recommendations for the format and content of physiologically based pharmacokinetic (PBPK) analyses submitted to the FDA to support applications including INDs, NDAs, BLAs, and ANDAs.  The guidance recognizes that while PBPK analyses can support decisions about clinical pharmacology studies and dosing recommendations, regulatory guidance is lacking for PBPK analysis reports, which causes significant variation in their format and content.  The guidance seeks to standardize the content and format of PBPK analysis reports to assist the FDA's regulatory review.

The FDA suggests sponsors include six sections in the report for all PBPK analyses and identifies specific information to include in each section:  Executive Summary, Introduction, Materials and Methods, Results, Discussion, and Appendices.  The Materials and Methods section should include sufficient information for FDA reviewers to duplicate and evaluate the modeling and simulation results, such as an overview of the modeling strategy, specification and justification of modeling parameters, a description of simulation conditions, electronic files related to modeling and software simulations, and specific software information.  The Results section should demonstrate that the PBPK model is appropriate and describe the results of model application.  It should present results from the methods used to verify the model, confirm model results, and conduct sensitivity analyses, and should discuss procedures used for model verification in the form of tables, graphs, and text where appropriate.  The Discussion section should explain how the PBPK modeling and simulation analyses adequately address the proposed scientific, regulatory, or clinical questions, and discuss and justify any proposed dosing recommendations based on the totality of evidence.  In the Appendices, the FDA recommends including a List of Tables, List of Figures, Table of Acronyms and Abbreviations, and References.

Readers are encouraged to read the final guidance, also available on the FDA's website.

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