An IQ Consortium Perspective on the FDA Guidance for Assessment of Pharmacokinetics in Participants With Impaired Renal Function

The FDA published guidance on assessing pharmacokinetics (PK) in participants with impaired renal function in 2024. The IQ CPLG Organ Impairment Working Group summarized the industry's perspective on this guidance by highlighting a few key updates in the 2024 guidance, including: (1) the recommendation of using estimated glomerular filtration rate (eGFR) over the Cockcroft-Gault (CG) equation to determine renal function; (2) the designs for dedicated renal impairment studies; and (3) characterizing the impact of impaired renal impairment in phase 2/3 trials. The use of absolute eGFR for dosing recommendations, differentiation between intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) in study design, and a preference for regression analysis over categorical analysis to model the relationship between renal function and PK parameters were also discussed. The updates in the FDA guidance resulted in better alignment with the European Medicines Agency (EMA) guidance on this topic, making global drug development more efficient. The manuscript also presented challenges in using different eGFR equations, the impact of protein binding on dose determination, and the need for further guidance on pediatric equations and novel drug modalities. In conclusion, the manuscript underscores the significance of the updated FDA guidance in enhancing the design, implementation, and data analysis of renal impairment studies while identifying areas for future updates to address emerging topics in drug development.