Evaluation of Truncated AUC as an Alternative Measure to Assess Pharmacokinetic Comparability in Bridging Biologic-Device Using Prefilled Syringes and Autoinjectors.

Pharmacokinetic (PK) comparisons between therapeutic biologics have largely been based on the total area under the concentration-time curve (AUC) and the maximum concentration (C ). For biologics with a long half-life, a PK comparability study may be long in duration and costly to conduct. The goal of this study was to evaluate whether a truncated AUC (tAUC) can be used to assess PK comparability when bridging prefilled syringe (PFS) and autoinjector (AI) treatment options for biologics with a long half-life. Fifteen biologics license applications (BLAs) were included to determine the concordance and geometric percent coefficient of variation (%CV) between tAUCs evaluated on days 7, 14, 21, and 28 and AUC evaluated to infinity (AUC ). Concordance is established if the tAUCs are comparable with AUC . Trial simulation was performed to examine the effect of the absorption rate constant (k ) and sample size on the concordance of tAUCs. The tAUCs evaluated on day 14, 21, and 28 had 100% concordance with AUC for all 15 BLAs. The concordance of tAUC evaluated at day 7 was 87.5%. Based on the trial simulation, tAUC evaluated to day 28 post-dose can achieve high concordance (≥85%) for biologics exhibiting linear or nonlinear elimination with a k of ≥0.1/day and with a sample size of 70 subjects per arm. tAUC appears to be a promising alternative PK measure, relative to AUC , for PK comparability assessments.