Protein aggregation and immunogenicity of biotherapeutics
DOI
10.1016/j.ijpharm.2020.119523
Document Type
Journal Article
Publication Date
7-30-2020
Publication Title
International Journal of Pharmaceutics
Volume
585
ISSN
3785173
Keywords
Anti-drug, Antibodies, Bioprocessing, High-concentration protein formulations, Monoclonal antibodies, T cell epitopes
Abstract
Recombinant proteins are the mainstay of biopharmaceuticals. A key challenge in the manufacturing and formulation of protein biologic products is the tendency for the active pharmaceutical ingredients to aggregate, resulting in irreversible drug loss, and an increase in immunogenicity risk. While the molecular mechanisms of protein aggregation have been discussed extensively in the literature, knowledge gaps remain in connecting the phenomenon in the context of immunogenicity of biotherapeutics. In this review, we discussed factors that drive aggregation of pharmaceutical recombinant proteins, and highlighted methods of prediction and mitigation that can be deployed through the development stages, from formulation to bioproduction. The purpose is to stimulate new dialogs that would bridge the interface between physical characterizations of protein aggregates in biotherapeutics and the functional attributes of the immune system.
Open Access
Green Accepted
Preprint
Repository Citation
Pham, N., & Meng, W. (2020). Protein aggregation and immunogenicity of biotherapeutics. International Journal of Pharmaceutics, 585. https://doi.org/10.1016/j.ijpharm.2020.119523