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Title: | Multi-criteria manufacturability indices for ranking high-concentration monoclonal antibody formulations |
Authors: | Yang, Y Velayudhan, A Thornhill, NF Farid, SS |
Keywords: | data mining;high-concentration mAb formulation;manufacturability index;viscosity;aggregation;developability assessment |
Issue Date: | 1-Sep-2017 |
Publisher: | Wiley |
Citation: | Yang, Y., Velayudhan, A., Thornhill, N.F. and Farid, S.S. (2017) 'Multi-criteria manufacturability indices for ranking high-concentration monoclonal antibody formulations', Biotechnology and Bioengineering, 2017, 114 (9), pp. 2043 - 2056. doi: 10.1002/bit.26329. |
Abstract: | Copyright © 2017 The Authors. The need for high-concentration formulations for subcutaneous delivery of therapeutic monoclonal antibodies (mAbs) can present manufacturability challenges for the final ultrafiltration/diafiltration (UF/DF) step. Viscosity levels and the propensity to aggregate are key considerations for high-concentration formulations. This work presents novel frameworks for deriving a set of manufacturability indices related to viscosity and thermostability to rank high-concentration mAb formulation conditions in terms of their ease of manufacture. This is illustrated by analyzing published high-throughput biophysical screening data that explores the influence of different formulation conditions (pH, ions, and excipients) on the solution viscosity and product thermostability. A decision tree classification method, CART (Classification and Regression Tree) is used to identify the critical formulation conditions that influence the viscosity and thermostability. In this work, three different multi-criteria data analysis frameworks were investigated to derive manufacturability indices from analysis of the stress maps and the process conditions experienced in the final UF/DF step. Polynomial regression techniques were used to transform the experimental data into a set of stress maps that show viscosity and thermostability as functions of the formulation conditions. A mathematical filtrate flux model was used to capture the time profiles of protein concentration and flux decay behavior during UF/DF. Multi-criteria decision-making analysis was used to identify the optimal formulation conditions that minimize the potential for both viscosity and aggregation issues during UF/DF. |
URI: | https://bura.brunel.ac.uk/handle/2438/24458 |
DOI: | https://doi.org/10.1002/bit.26329 |
ISSN: | 0006-3592 |
Appears in Collections: | Chemistry |
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