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. 2023 Dec;63(12):1417-1429.
doi: 10.1002/jcph.2322. Epub 2023 Aug 25.

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

Ya-Feng Wen  1 , Ping Ji  1 , Sarah J Schrieber  2 , Sneha Rathi  1 , Delaney McGuirt  1 , Jiang Liu  3 , Jianmeng Chen  1 , Yow-Ming Wang  4 , Suresh Doddapaneni  1 , Chandrahas Sahajwalla  1
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Evaluation of Truncated AUC as an Alternative Measure to Assess Pharmacokinetic Comparability in Bridging Biologic-Device Using Prefilled Syringes and Autoinjectors

Ya-Feng Wen et al. J Clin Pharmacol. 2023 Dec.

Abstract

Pharmacokinetic (PK) comparisons between therapeutic biologics have largely been based on the total area under the concentration-time curve (AUC) and the maximum concentration (Cmax ). 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 (AUC0-inf ). Concordance is established if the tAUCs are comparable with AUC0-inf . Trial simulation was performed to examine the effect of the absorption rate constant (ka ) and sample size on the concordance of tAUCs. The tAUCs evaluated on day 14, 21, and 28 had 100% concordance with AUC0-inf 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 ka 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 AUC0-inf , for PK comparability assessments.

Keywords: PK comparability; biologics; noncompartmental analysis; study design; truncated AUC.

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