Early prediction of formulation behaviour for new antibody products

Lead Research Organisation: Imperial College London
Department Name: Department of Chemical Engineering

Abstract

Antibody-based biologics such as monoclonal antibodies (mAbs) are a fast-growing segment of the biopharmaceutical industry due to their distinctive therapeutic potential. The global market for antibody-based therapeutics is forecasted to reach $114.6 billion by 2022 growing at a compound annual growth rate (CAGR) of 6.3% from 2017 to 2022 (Dewan, 2017). In contrast to traditional small molecule drugs, mAbs have high levels of specificity with low toxicity profiles, which drives their success in targeting previously untreatable indications (Keizer et al, 2010). Consequently, there has been a rise in research interest in developing novel mAb therapies and biosimilars.
Formulation development remains a major challenge in mAb production as there is a high demand to formulate therapeutics economically and effectively for safe delivery to patients. The increased complexity of these large molecule makes them more unstable and prone to chemical and/or physical degradation, therefore requiring special handling and storage. Lyophilisation, or freeze drying is a common method used in industry to preserve chemical and biological properties of mAbs to sustain long-term stability and improve shelf life (Carpenter et al, 2002). Protein aggregation is a common problem that can occur at any stage of the manufacturing process up until drug administration. Not only can aggregation affect protein function and decrease product yield, it can also reduce the therapeutic half-life and cause immunogenic reactions in patients (Wang et al, 2007).
Previous work at SPEL have uncovered the relationship between the Osmotic second virial coefficient (B22) obtained from self-interaction chromatography (SIC) and propensity of mAb aggregation (Hedberg et al, 2018). The aim of the project is to further investigate aggregation propensity of liquid and lyophilised biotherapeutics and understand the mechanisms of aggregation to help predict aggregation tendencies of novel mAbs. In addition to extensive structural characterisation, functionality will be investigated to assess biological activity and immunogenicity.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011178/1 01/10/2015 30/09/2023
2367694 Studentship BB/M011178/1 30/09/2019 30/09/2023 Kam Yenh Hua