A Cell-Based Reporter Gene Assay for TNF-α Neutralization: Analytical Qualification and Application to Adalimumab and Its Biosimilars.

IF 4.3 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Pharmaceutical Research Pub Date : 2026-05-05 DOI:10.1007/s11095-026-04093-5

Christelle Anne F Ancajas, Shen Luo, Baolin Zhang

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引用次数: 0

Abstract

Purpose: To qualify a mechanism-of-action (MoA)-reflective reporter gene assay (RGA) for measuring the biological activity of adalimumab (Humira) and its biosimilars, supporting assessment of product quality, comparability, and functional consistency across the product lifecycle.

Methods: The assay evaluates TNF-α neutralization by monitoring inhibition of NF-κB signaling in a reporter system. Qualification focused on key performance attributes, including system suitability, working range, reproducibility, and intermediate precision, to confirm fitness for routine use.

Results: The RGA yielded MoA-relevant readouts of NF-κB pathway inhibition in the presence of adalimumab, demonstrating strong system suitability, a broad working range, high reproducibility, and consistent intermediate precision across repeated measures. These characteristics support reliable measurement of functional activity among adalimumab products and biosimilars.

Conclusions: The qualified, MoA-reflective RGA provides a robust tool for lifecycle management of adalimumab products, enabling quality assessment, comparability exercises, and monitoring of functional consistency across indications in which adalimumab is broadly used (e.g., rheumatoid arthritis, Crohn's disease, psoriasis).

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基于细胞的TNF-α中和报告基因测定：阿达木单抗及其生物类似药的分析鉴定和应用。

目的：验证用于测量阿达木单抗（Humira）及其生物仿制药生物活性的作用机制（MoA）反射报告基因测定（RGA），支持评估产品质量、可比性和整个产品生命周期的功能一致性。方法：该试验通过监测报告系统中NF-κB信号的抑制来评估TNF-α中和作用。确认关注关键性能属性，包括系统适用性、工作范围、可重复性和中间精度，以确认适合日常使用。结果：在阿达木单抗存在下，RGA获得了与moa相关的NF-κB通路抑制读数，显示出较强的系统适用性、较宽的工作范围、高重现性以及在重复测量中一致的中间精度。这些特征支持阿达木单抗产品和生物类似药之间功能活性的可靠测量。结论：合格的、反映moa的RGA为阿达木单抗产品的生命周期管理提供了一个强大的工具，可以进行质量评估、可比性练习和监测阿达木单抗广泛使用的适应症（如类风湿关节炎、克罗恩病、牛皮癣）的功能一致性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.