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DC Field | Value | Language |
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dc.contributor.author | Yang, Y | - |
dc.contributor.author | Velayudhan, A | - |
dc.contributor.author | Thornhill, NF | - |
dc.contributor.author | Farid, SS | - |
dc.date.accessioned | 2022-04-20T13:32:12Z | - |
dc.date.available | 2022-04-20T13:32:12Z | - |
dc.date.issued | 2017-09-01 | - |
dc.identifier.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. | en_US |
dc.identifier.issn | 0006-3592 | - |
dc.identifier.uri | https://bura.brunel.ac.uk/handle/2438/24458 | - |
dc.description.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. | en_US |
dc.description.sponsorship | UK Engineering & Physical Sciences Research Council (EPSRC) for the EPSRC Centre for Innovative Manufacturing in Emergent Macromolecular Therapies. Grant Number: EP/I033270/1; Consortium of Industrial and Governmental Users. | en_US |
dc.format.extent | 2043 - 2056 | - |
dc.language | English | - |
dc.language.iso | en_US | en_US |
dc.publisher | Wiley | en_US |
dc.rights | © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Perodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.subject | data mining | en_US |
dc.subject | high-concentration mAb formulation | en_US |
dc.subject | manufacturability index | en_US |
dc.subject | viscosity | en_US |
dc.subject | aggregation | en_US |
dc.subject | developability assessment | en_US |
dc.title | Multi-criteria manufacturability indices for ranking high-concentration monoclonal antibody formulations | en_US |
dc.type | Article | en_US |
dc.identifier.doi | https://doi.org/10.1002/bit.26329 | - |
dc.relation.isPartOf | Biotechnology and Bioengineering | - |
pubs.issue | 9 | - |
pubs.publication-status | Published | - |
pubs.volume | 114 | - |
Appears in Collections: | Chemistry |
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