FDA Announces Availability of the Final Guidance, “Physiologically Based Pharmacokinetic Analyses — Format and Content”

On September 4, 2018, the U.S. Food and Drug Administration (FDA) announced the availability of the final guidance entitled “Physiologically Based Pharmacokinetic Analyses — Format and Content.” This guidance outlines the recommended format and content of Physiologically Based Pharmacokinetic (PBPK) data and analyses submitted in Investigational New Drug (IND) applications, New Drug Applications (NDA), Biologics License Applications (BLA), and Abbreviated New Drug Applications (ANDA) to enable efficient and consistent FDA review. 

A PBPK analysis uses models and simulations that combine physiology, population, and drug characteristics to mechanistically describe the pharmacokinetic (PK) and/or pharmacodynamic behavior of a drug. Throughout a drug’s life cycle, PBPK model predictions can be used to support decisions on whether, when, and how to conduct certain clinical pharmacology studies, and to support dosing recommendations in product labeling. Because of the lack of regulatory guidance, the format and content of PBPK analysis reports that are submitted to FDA vary significantly. The goal of this guidance is to standardize the content and format of these reports to facilitate FDA’s efficient assessment, consistent application, and timely decision making during regulatory review. To enable efficient and consistent review, FDA recommends including the following six sections in a PBPK study report: (A) Executive Summary, (B) Introduction, (C) Materials and Methods, (D) Results, (E) Discussion, and (F) Appendices.

This guidance does not address methodological considerations and best practices for the conduct of PBPK modeling and simulation or the appropriateness of PBPK analyses for a particular drug or drug product. The decision to accept results from PBPK analyses in lieu of clinical PK data is made on a case-by-case basis, considering the intended uses, as well as the quality, relevance, and reliability of the results from the PBPK analyses.

As PBPK models are highly complex in nature, sponsors anticipating the application of PBPK modeling in their drug development program should communicate early with FDA.

The “Physiologically Based Pharmacokinetic Analyses — Format and Content” final guidance is available at https://go.usa.gov/xP3SU.

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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.