Abstract
Parenteral products appear to be sensitive to process conditions in bioprocessing steps, such as interfacial stress and shear stress. The combination of these elements is widely believed and proven to influence product stability, but the defined roles of these players in the product damage process have not yet been identified. The present work addresses a current industrial problem, by focusing on the analysis of shear stress on protein-based therapeutics flowing in tubing by means of Computational Fluid Dynamics simulations. The purpose of this article is not to pinpoint the mechanism triggering the damage of the product, but it represents the first step towards wider experimental investigations and introduces a new strategy to quantify the average shear stress. The field of scale-down approaches, used to scale the commercial process down to the laboratory level, is also explored. Since quality control is critical in the pharmaceutical realm, it is essential that the scale-down approach preserves the same stress exposure as the commercial scale, which in the present work is considered to be that resulting from shear effects. Therefore, a new approach for scaling down the commercial process is proposed, which has been compared with traditional approaches and shown to provide greater representativeness between the two scales.