Impact of protein adsorption during biopharmaceutical manufacture & storage
John Donal Downey, Abina M. Crean, Katie B. Ryan
Abstract
Protein therapeutics contact multiple interfaces during formulation, filtration, fill-finish, and storage processes. Interactions at these interfaces can compromise the conformational and colloidal stability of therapeutic proteins through surface adsorption, potentially leading to aggregation and particle formation. Surface-induced conformational changes in protein higher-order structures, influenced by interfacial hydrophobicity and charge, are key drivers of these effects. The resulting loss of active protein and increased aggregation risk pose significant challenges to the efficacy and safety of the final biotherapeutic product. Thus, it is imperative to develop strategies that minimize protein-surface interactions that may compromise the protein's conformational and colloidal stability during manufacture and storage. This review focuses on current research related to the adsorption behaviour of biotherapeutics at interfaces encountered during fill-finish and storage. Furthermore, the review introduces the factors influencing protein adsorption and interfacial stability and current methodologies and advancements in mitigating interfacial adsorption, emphasizing rational formulation design strategies. Synopsis Protein adsorption during commercial biopharmaceutical operations such as mixing, filtration and fill pumping has been identified as a root cause of protein particle formation in liquid parenteral protein products. Further, excipient-packaging incompatibilities contribute to silicone oil contamination and protein-polydimethylsiloxane particle formation. Intrinsic protein and excipient instability can be linked to buffer composition, pH and tonicity. Simple addition of surfactants does not guarantee protein stabilization and scope exists for the development of innovative protein formulations and packaging materials.