@article{Yang:2017:10.1002/bit.26329,
author = {Yang, Y and Velayudhan, A and Thornhill, NF and Farid, SS},
doi = {10.1002/bit.26329},
journal = {Biotechnology and Bioengineering},
pages = {2043--2056},
title = {Multi-criteria manufacturability indices for ranking high-concentration monoclonal antibody formulations},
url = {http://dx.doi.org/10.1002/bit.26329},
volume = {114},
year = {2017}
}

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TY  - JOUR
AB  - 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 analysing 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 behaviour 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.
AU  - Yang,Y
AU  - Velayudhan,A
AU  - Thornhill,NF
AU  - Farid,SS
DO  - 10.1002/bit.26329
EP  - 2056
PY  - 2017///
SN  - 1097-0290
SP  - 2043
TI  - Multi-criteria manufacturability indices for ranking high-concentration monoclonal antibody formulations
T2  - Biotechnology and Bioengineering
UR  - http://dx.doi.org/10.1002/bit.26329
UR  - http://hdl.handle.net/10044/1/48415
VL  - 114
ER  - 

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