Computational fluid dynamic simulations of temperature, cryoconcentration, and stress time during large-scale freezing and thawing of monoclonal antibody solutions

Bluemel, Oliver; Pavlišič, Andraž; Likozar, Blaž; Rodrigues, Miguel A.; Bechtold-Peters, Karoline; Frieß, Wolfgang

doi:10.1016/j.ejpb.2022.06.007

Cited by 2 publications

(1 citation statement)

References 5 publications

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“…The authors went on to show that the protein and small excipients freeze-concentrate differently, resulting in different local protein to stabilizer ratios within a container, ultimately leading to mAb instability under these storage conditions. 18 Interestingly, Bluemel et al 19 have recently reported on the use of computational fluid dynamic (CFD) simulations of mAb solutions. They conclude that CFD simulations are a promising tool to describe large-scale freezing and thawing of mAb solutions and could potentially save time and resources.…”

Section: Aggregationmentioning

confidence: 99%

High concentration formulation developability approaches and considerations

Zarzar¹,

Khan

Bhagawati³

et al. 2023

mAbs

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The growing need for biologics to be administered subcutaneously and ocularly, coupled with certain indications requiring high doses, has resulted in an increase in drug substance (DS) and drug product (DP) protein concentrations. With this increase, more emphasis must be placed on identifying critical physico-chemical liabilities during drug development, including protein aggregation, precipitation, opalescence, particle formation, and high viscosity. Depending on the molecule, liabilities, and administration route, different formulation strategies can be used to overcome these challenges. However, due to the high material requirements, identifying optimal conditions can be slow, costly, and often prevent therapeutics from moving rapidly into the clinic/market. In order to accelerate and derisk development, new experimental and in-silico methods have emerged that can predict high concentration liabilities. Here, we review the challenges in developing high concentration formulations, the advances that have been made in establishing low mass and high-throughput predictive analytics, and advances in in-silico tools and algorithms aimed at identifying risks and understanding high concentration protein behavior.

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Section: Aggregationmentioning

confidence: 99%