FDA Issues Draft Guidance on PBPK Analysis

US regulatory authority Food and Drug Administration (FDA) on 1st December 2016 released a new draft guidance designed to assist sponsors report physiologically based pharmacokinetic (PBPK) analyses to the agency in a standard format.

PBPK Analyses

With respect to FDA, “PBPK analysis makes use of models and simulations that combine physiology, population, and drug characteristics to mechanistically explain the pharmacokinetic (PK) and/or pharmacodynamic (PD) behaviors of a drug.”

These analyses, FDA states, can also notify other choices about future clinical pharmacology studies and dosing suggestions, and are usually used to support investigational new drug applications (INDs), new drug applications (NDAs), biologics license applications (BLAs) and abbreviated new drug applications (ANDAs).

Draft Guidance

“Due to the lack of regulatory guidance, the format and content of PBPK analyses that are presented to the FDA differ considerably across drug developers,” FDA writes.

Therefore, FDA states it was essential to standardize the format and content of PBPK study reports to be able to boost the agency’s performance and consistency in evaluating them.

In the draft guidance, FDA suggests a six-part structure for PBPK study reports that consists of a section for an

  • executive summary,
  • introduction
  • materials and methods
  • results,
  • discussion and
  • appendices


However, FDA understands that the quantity of data provided in each section will vary considerably based on when the studies are done, FDA says it still suggests finishing each of the sections based on the data accessible.

In addition, the section on materials and methods is additional broken down into five sub-sections:

  • Overview of modeling strategy
  • Modeling parameters
  • Simulation design
  • Electronic files and other documentation
  • Software

While FDA does not have any particular requirements for the software applied in PBPK modeling, the FDA asks that sponsors send details on the software they have selected in a table.