Cavitation in Pharmaceutical Manufacturing and Shipping

Therapeutic proteins are used to successfully treat hemophilia, Crohn’s Disease, diabetes, and cancer. Recent product recalls have occurred because of sub-visible particle formation resulting from the inherent instability of proteins. It has been suggested that particle formation is associated with late stage processing steps of filling, shipping, and delivery. Previous work at the University of Denver demonstrated that fluid cavitation can generate a large number of sub-visible protein particles in ultra clean formulations, but that mitigation can be achieved with fluid property manipulation. The goal of this research was to (1) assess the risk of cavitation under common pharmaceutical manufacturing conditions (i.e., pipe contraction and pumps), (2) establish a simple threshold criterion, and (3) suggest a series of mitigation techniques based on these thresholds. To accomplish these tasks, computational fluid dynamic simulations for a variety of pipe contraction and vial drop conditions were performed. The impact of geometry, fluid properties and operating conditions were varied to establish thresholds and mitigation strategies. The results of this research show that reducing the turbulence in a fluid system will cause the fluid to be less likely to cavitate. Additionally, threshold bounds were created that establish a definitive transition at which cavitation will occur.