Physicochemical factors of bioprocessing impact the stability of therapeutic proteins.

The aggregation of therapeutic proteins is potentially encountered during various steps such as bioprocessing, formulation, storage, transportation and administration. The aggregation results in irreversible drug loss and also leads to an increase in the risk of immunogenicity. The aggregated proteins have also been associated with various protein deposition diseases like amyloidosis. Various physicochemical factors like pH, temperature, salt concentrations, ionic strength, shear and surface affect the stability of proteins. Interestingly, therapeutic proteins simultaneously experience these physical, chemical and mechanical stresses during upstream, downstream and storage processes. The above physicochemical factors are reported to induce the unfolding and aggregation of proteins. The mechanistic insights of this complex aggregation behavior may allow devising strategies to limit/restrict this unwanted phenomenon. This review intends to undertake systematic descriptions of the key physicochemical factors in upstream and downstream bioprocesses and correlating their implications with the unfolding and aggregation of therapeutic proteins. The present review highlights the impacts of environmental, chemical and mechanical factors of the bioprocessing on the stability/aggregation of therapeutic proteins. The present review offers insight into this important phenomenon, which will be helpful for real-world challenges in the bioprocess and bio-therapeutic industries.