FDA Issues Final Guidance on Physiologically-Based Pharmacokinetic Analyses

The FDA released final guidance Tuesday for drug sponsors on the content and formatting of physiologically-based pharmacokinetic (PBPK) analyses, including an expanded section on formatting and a simplified section on software.

The agency said any analysis should explain how the PBPK modeling and simulation address clinical, scientific and regulatory questions, adding that the “basis for any requests to waive the conduct of clinical studies should be discussed and well substantiated.”

If simulations are used to support specific dosing recommendations tested in future clinical trials or incorporated into prescription drug labeling, the proposed doses should be “discussed and justified within the totality of evidence, including the context of known exposure-response relationships and the level of confidence in the PBPK model for its intended uses,” the guidance states.