Impact of protein adsorption during biopharmaceutical manufacture & storage

IF 4.3 3区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutical Sciences Pub Date : 2025-03-15 DOI:10.1016/j.ejps.2025.107071

John D. Downey, Abina M. Crean, Katie B. Ryan

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Abstract

Protein therapeutics contact multiple interfaces during formulation, filtration, fill-finish, and storage processes. Interactions at these interfaces can compromise the conformational and colloidal stability of therapeutic proteins through surface adsorption, potentially leading to aggregation and particle formation. Surface-induced conformational changes in protein higher-order structures, influenced by interfacial hydrophobicity and charge, are key drivers of these effects. The resulting loss of active protein and increased aggregation risk pose significant challenges to the efficacy and safety of the final biotherapeutic product. Thus, it is imperative to develop strategies that minimize protein-surface interactions that may compromise the protein's conformational and colloidal stability during manufacture and storage. This review focuses on current research related to the adsorption behaviour of biotherapeutics at interfaces encountered during fill-finish and storage. Furthermore, the review introduces the factors influencing protein adsorption and interfacial stability and current methodologies and advancements in mitigating interfacial adsorption, emphasizing rational formulation design strategies.

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生物制药生产和储存过程中蛋白质吸附的影响。

蛋白质治疗剂在配方、过滤、填充和储存过程中接触多个界面。这些界面上的相互作用会通过表面吸附损害治疗蛋白的构象和胶体稳定性，潜在地导致聚集和颗粒形成。受界面疏水性和电荷影响的蛋白质高阶结构的表面诱导构象变化是这些效应的关键驱动因素。由此导致的活性蛋白的损失和聚集风险的增加对最终生物治疗产品的有效性和安全性构成了重大挑战。因此，必须制定策略，最大限度地减少蛋白质表面相互作用，这些相互作用可能在制造和储存过程中损害蛋白质的构象和胶体稳定性。本文综述了生物治疗药物在填充和储存过程中所遇到的界面上的吸附行为。此外，综述了影响蛋白质吸附和界面稳定性的因素以及减少界面吸附的现有方法和进展，强调了合理的配方设计策略。

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

European Journal of Pharmaceutical Sciences 医学-药学

CiteScore

9.60

自引率

2.20%

发文量

248

审稿时长

50 days

期刊介绍： The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.