Real-time imaging of monoclonal antibody film reconstitution after mechanical stress at the air-liquid interface by Brewster angle microscopy

Žuntar, Timotej; Ličen, Matjaž; Kuzman, Drago; Osterman, Natan

doi:10.1016/j.colsurfb.2022.112757

Cited by 3 publications

(1 citation statement)

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“…To study the aggregation of large particles, new methods have been developed that borrow from the physical and life sciences. For example, a method for assessing the aggregation of mAbs on the water–air surface based on Brewster angle microscopy was recently presented [ 8 ]. A large class of methods particularly suitable for large particles is based on microfluidics [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Real-Time Assessment of the Size Changes of Individual Sub-Visible Protein Particles under Buffer Variations: A Microfluidic Study

Kuzman,

Klančnik,

Grum

et al. 2023

Pharmaceuticals

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Protein particles in biological drugs can significantly impact drug efficacy and carry the risk of adverse effects. Despite advancements, the understanding and control of particle formation in biopharmaceutical manufacturing remain incomplete. Therefore, further investigation into protein particles is warranted, especially considering that novel formats of biological drugs may be more susceptible to aggregation and particle formation than conventional monoclonal antibodies. In this study, we introduce a microfluidic approach for the real-time analysis of individual sub-visible protein particles during buffer exchange. We find that the modulation of intermolecular forces, achieved by changing the buffer pH or urea concentration, leads to the reversible swelling and shrinkage of particles by up to 50%, which is a consequence of altered intermolecular distances. Additionally, we identify a discrepancy in the biophysical behavior of protein particles compared to monomeric protein. This finding highlights the limited predictive power of commonly applied biophysical characterization methods for particle formation in early formulation development. Moreover, the observed particle swelling may be associated with manufacturing deviations, such as filter clogging. These results highlight the importance of studying individual particles to gain a comprehensive insight into particle behavior and the impact of formulation variations in the biopharmaceutical industry.

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