Assessing subvisible particle risks in monoclonal antibodies: insights from quartz crystal microbalance with dissipation, machine learning, and in silico analysis DOI Creative Commons

Yibo Wang,

Alexis Hanford,

Mehdi Boroumand

и другие.

mAbs, Год журнала: 2025, Номер 17(1)

Опубликована: Май 11, 2025

Throughout the lifecycle of biopharmaceutical development and manufacturing, monoclonal antibodies (mAbs) are subjected to diverse interfacial stresses encounter various container surfaces. These interactions can cause formation subvisible particles (SVPs) that complicate developability stability assessments drug products. This study leverages quartz crystal microbalance with dissipation (QCM-D), an characterization technique, as well both in silico experimentally measured physicochemical properties, investigate significant differences SVP among different mAbs due stresses. We conducted forced degradation experiments borosilicate glass high-density polyethylene containers, using agitation stirring rank 15 on risks. Our data indicate kinetics antibody adsorption solid-liquid interfaces correlate strongly propensity yet show a weaker correlation agitation-induced SVPs. In addition, morphology was analyzed self-supervised machine learning flow imaging microscopy images. Despite differing surface chemistry two types, resulted similar morphologies, contrast unique morphologies produced by agitation. Collectively, our research demonstrates utility QCM-D models evaluating mAb their tendency form interface-mediated SVPs, providing strategy mitigate risks associated biotherapeutic development.

Язык: Английский

Polysorbates degrading enzymes in biotherapeutics – a current status and future perspectives DOI Creative Commons

Marius Nicolaus Felix,

Thomas Waerner,

Dániel Lakatos

и другие.

Frontiers in Bioengineering and Biotechnology, Год журнала: 2025, Номер 12

Опубликована: Янв. 10, 2025

Polysorbates, in particular polysorbate (PS) 20 and 80, are the most commonly used surfactants for stabilising biotherapeutics produced by biotechnological processes. PSs derived from ethoxylated sorbitan (a derivative of sorbitol) esterified with fatty acids varying chain length degree saturation. In past, these have been reported to specific liabilities. Chemical (oxidations hydrolyses) enzymatic degradations affect stability PS drug products. Specifically, presence trace amounts (sub-ppm) certain host cell proteins (HCPs) can induce degradation, which lead release free during storage over time. Enzymatic degradation may impair functionality surfactant therapeutic proteins, leading formation visible and/or sub-visible particles biopharmaceutical This review summarises enzymes currently known be involved mammalian processes proteins. recent years, advanced analytical methods developed qualify quantify PS-degrading enzymes. Most assays based on mass spectrometry a preceding HCP enrichment approach. Efforts were made measure enzyme activity correlate it observed degradation. The impact product quality attributes, including acid solubility phase separation, up particles, potential induction protein protein/fatty mixed as well sensitivity towards was considered. Various substance (DS) mitigation strategies related occurrence degrading discussed amongst them generation stable knockout lines, also carefully analysed. underlying opinion article reflects undergoing discussions focusses (i) product, (ii) analytics identification/quantification (characterisation) enzymes, (iii) (iv) identified (v) avoid DS manufacturing.

Язык: Английский

Процитировано

2
Impact of Protein Adsorption During Biopharmaceutical Manufacture & Storage DOI Creative Commons

John Donal Downey,

Abina M. Crean, Katie B. Ryan

и другие.

European Journal of Pharmaceutical Sciences, Год журнала: 2025, Номер unknown, С. 107071 - 107071

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Assessing subvisible particle risks in monoclonal antibodies: insights from quartz crystal microbalance with dissipation, machine learning, and in silico analysis DOI Creative Commons

Yibo Wang,

Alexis Hanford,

Mehdi Boroumand

и другие.

mAbs, Год журнала: 2025, Номер 17(1)

Опубликована: Май 11, 2025

Throughout the lifecycle of biopharmaceutical development and manufacturing, monoclonal antibodies (mAbs) are subjected to diverse interfacial stresses encounter various container surfaces. These interactions can cause formation subvisible particles (SVPs) that complicate developability stability assessments drug products. This study leverages quartz crystal microbalance with dissipation (QCM-D), an characterization technique, as well both in silico experimentally measured physicochemical properties, investigate significant differences SVP among different mAbs due stresses. We conducted forced degradation experiments borosilicate glass high-density polyethylene containers, using agitation stirring rank 15 on risks. Our data indicate kinetics antibody adsorption solid-liquid interfaces correlate strongly propensity yet show a weaker correlation agitation-induced SVPs. In addition, morphology was analyzed self-supervised machine learning flow imaging microscopy images. Despite differing surface chemistry two types, resulted similar morphologies, contrast unique morphologies produced by agitation. Collectively, our research demonstrates utility QCM-D models evaluating mAb their tendency form interface-mediated SVPs, providing strategy mitigate risks associated biotherapeutic development.

Язык: Английский

Процитировано

0