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Multi-criteria manufacturability indices for ranking high-concentration monoclonal antibody formulations

Yang, Y; Velayudhan, A; Thornhill, NF; Farid, SS; (2017) Multi-criteria manufacturability indices for ranking high-concentration monoclonal antibody formulations. Biotechnology and Bioengineering , 114 (9) pp. 2043-2056. 10.1002/bit.26329. Green open access

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Abstract

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.

Type: Article
Title: Multi-criteria manufacturability indices for ranking high-concentration monoclonal antibody formulations
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/bit.26329
Publisher version: http://doi.org/10.1002/bit.26329
Language: English
Additional information: Copyright © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Perodicals, Inc. This is an open access article under the terms of the Creative Commons AttributionLicense, which permits use, distribution and reproduction in any medium, provided theoriginal work is properly cited.
Keywords: data mining; high-concentration mAb formulation;manufacturability index; viscosity; aggregation; developabilityassessment
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/1555808
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