Evaluation of the performance of polysorbates variants on the stability of monoclonal antibody therapeutics

Lead Research Organisation: University of Manchester
Department Name: School of Health Sciences

Abstract

Manufacturing of biopharmaceuticals, one of the fastest growing areas of the pharmaceutical industry, often suffers from protein aggregation and particle formation. Protein aggregation not only reduces the efficiency of upstream bioprocessing stages, but also may increase the immunogenicity of biopharmaceuticals. Thus, following bioprocess, monoclonal antibodies (mAbs) are formulated as solutions in presence of different excipients designed to guarantee their stability and to prevent mAbs degradation or aggregation over time, or during storage and transport. Polysorbates are non-ionic surfactants widely used by the industry, adsorbing at the interfaces of the container (wall/solution and air/solution) to limit undesired conformational changes of mAbs and their subsequent aggregation. Although being widely used, there is a paucity of information on their expected formulation role and how the polysorbate characteristics and purity affect mAb stability.
This project aligns with the BBSRC science remit as it will develop tools which underpin biological research, namely in the area of mAb stability. This research may lead to development of improved biopharmaceutical production or improved efficacy and shelf-life of biopharmaceutical products or be further applied to other protein systems. This project will be carried out at the Manchester Institute of Biotechnology (MIB).
Project aims
The aim of the project is to explore the impact of polysorbate characteristics on the stability of mAbs and other biopharmaceutically-relevant protein models in solution, and to develop methodologies to assess this. This will be examined across Croda's different grades of polysorbates. Furthermore, the final aim is to explore how protein stability can be improved and maximised, leading to greater activity and / or shelf life extension of biopharmaceuticals. To meet these aims, the following objectives are proposed:
To develop and validate a method and its associated techniques assessing the stability of mAbs and other model proteins solutions following imposed stress (e.g. shaking, temperature)
To evaluate the influence of variances of currently used polysorbates on the stability of the mAb formulation
To correlate mAbs stability with the change in polysorbate

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/R505080/1 01/10/2017 30/09/2021
1945003 Studentship BB/R505080/1 01/10/2017 30/09/2021 Sam Chapman