Chapter 12: Strategies in the Development of Formulations for Antibody-Based Therapeutics

Jameel, Feroz; Moussa, Ehab M.; Mills, Brittney J.; Ihnát, Peter

doi:10.1007/978-3-030-31415-6_12

Cited by 1 publication

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“…Solution viscosity is a critical attribute for the development of high-concentration protein formulations, as an elevated viscosity (>30 cP) can significantly impact the pressure and flow in various unit operations such as filtration, ultrafiltration-diafiltration, and filling, 95 , 96 as well as limit the development of devices for drug administration (e.g., auto-injectors and pre-filled syringes). 186 From a physicochemical standpoint, it has been proposed that the presence of transient protein clusters is the root cause of high viscosity in protein solutions, which is in turn driven by protein–protein interactions. 187 , 188 As such, understanding the relationships between interactions, solution structure and solution rheology is key for establishing appropriate formulation strategies to achieve a suitable viscosity in high-concentration biotherapeutics.…”

Section: High-concentration Physical Instabilitiesmentioning

confidence: 99%

Computational models for studying physical instabilities in high concentration biotherapeutic formulations

Blanco

2022

mAbs

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Computational prediction of the behavior of concentrated protein solutions is particularly advantageous in early development stages of biotherapeutics when material availability is limited and a large set of formulation conditions needs to be explored. This review provides an overview of the different computational paradigms that have been successfully used in modeling undesirable physical behaviors of protein solutions with a particular emphasis on high-concentration drug formulations. This includes models ranging from all-atom simulations, coarse-grained representations to macro-scale mathematical descriptions used to study physical instability phenomena of protein solutions such as aggregation, elevated viscosity, and phase separation. These models are compared and summarized in the context of the physical processes and their underlying assumptions and limitations. A detailed analysis is also given for identifying protein interaction processes that are explicitly or implicitly considered in the different modeling approaches and particularly their relations to various formulation parameters. Lastly, many of the shortcomings of existing computational models are discussed, providing perspectives and possible directions toward an efficient computational framework for designing effective protein formulations.

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Section: High-concentration Physical Instabilitiesmentioning

confidence: 99%

Computational models for studying physical instabilities in high concentration biotherapeutic formulations

Blanco

2022

mAbs

View full text Add to dashboard Cite

show abstract

Chapter 12: Strategies in the Development of Formulations for Antibody-Based Therapeutics

Cited by 1 publication

References 44 publications

Computational models for studying physical instabilities in high concentration biotherapeutic formulations

Computational models for studying physical instabilities in high concentration biotherapeutic formulations

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