Background Analysis: US FDA Advisory Committee to Give Input on Renal Impairment and Drug Exposure; Translating PK Information into Dose Instructions – MAY 7, 2019 (ACPS-CP)

Announcement

The US FDA has scheduled a Pharmaceutical Science and Clinical Pharmacology Advisory Committee (ACPS-CP) meeting for Tuesday, May 7, 2019. The meeting will focus on two topics related to the Office of Pharmaceutical Quality's priority of promoting the availability of better medicine. The first topic will focus on approaches to evaluate the effect of renal impairment on drug exposure. The second topic will examine best practice considerations for translating pharmacokinetic (PK) information into dose individualization instructions.

Background and Agenda

Regarding the first topic, approaches to evaluate the effect of renal impairment on drug exposure, the FDA has provided background information in the Federal Register notice. The FDA notes that many registration trials exclude patients with advanced kidney disease, and product labeling dosing instructions for these patients are commonly derived from our understanding of the change in the PK in individuals with varying degrees of renal function. The most common current approach to determine dosing instructions for patients with varying degrees of renal function begins with a stand-alone renal impairment study, with either a full design or a reduced design. In addition to stand-alone renal impairment studies, drug development programs often use the findings from population PK (POPPK) analyses, which leverage the PK information across all the studies available in a drug development program. An alternative approach to consider is for drug development programs to predict the impact of renal impairment on the PK of the drug, either based on the understanding of the PK of a new molecular entity or using physiologic-based PK (PBPK) models, without a stand-alone renal impairment study. Patients with impaired renal function can then be included in later stage clinical trials, with prospective dose adjustment incorporated, if deemed necessary, based on the predictions. The dosing should be confirmed, based on analysis of PK samples from the late stage trials (sparse PK, POPPK analysis).

Regarding the second topic, best practice considerations for translating PK information into dose individualization instructions, the FDA says that dose individualization is typically achieved by applying the concept of ‘exposure-matching’ under the assumption that such a maneuver will result in a benefit-risk similar to that observed in the registration trials. The committee will discuss the application of ‘exposure matching,’ including the necessary assumptions and any limitations.

What’s Next?

Tarius will send a Briefing Summary after briefing materials are posted to FDA’s website (typically within 2 days of the meeting). This report will provide a summary of the FDA briefing materials.

Tarius will send a Results Wire soon after the meeting. This report will include the voting outcomes, if applicable, and key outcomes of the discussion.

METADATA: Sponsor: none Drug Name: none Drug Class: none Indication: none

For more information about SAC Tracker reports and other benefits for our subscribers, click here.

DISCLAIMER: The information in this document is for informational purposes only. The SAC Tracker Background Analysis contains information from publicly available sources, including FDA, sponsor, scientific, and clinical websites. Tarius A/S assumes no liability for any inaccurate or incomplete information, or for any actions taken in reliance thereon. © Tarius A/S. All rights reserved.