AU - Yang,Y AU - Velayudhan,A AU - Thornhill,NF AU - Farid,SS DO - 10.1002/bit. 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. A mathematical filtrate flux model was used to capture the time profiles of protein concentration and flux decay behaviour during UF/DF. 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.

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.

A decision tree classification method, CART (Classification and Regression Tree) is used to identify the critical formulation conditions that influence the viscosity and thermostability. 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. 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. Viscosity levels and the propensity to aggregate are key considerations for high-concentration formulations.

Download RIS format (EndNote, RefMan) 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.

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