LAUSR

Mechanical shock may cause cavitation in vials containing liquid formulations of therapeutic proteins and generate protein aggregates and other particulates. To test whether common formulation components such as protein molecules, air bubbles or polysorbate 20 (PS20) micelles might nucleate cavitation, a high-speed video camera was used to detect cavitation in vials containing antibody formulations following application of controlled mechanical shock using a shock test. Higher concentrations of sub-visible particles were found in formulations where cavitation had occurred. Bubbles trapped on vial surfaces were a primary site for cavitation nucleation; other potential cavitation nuclei were ineffective. The incidence of cavitation events observed following application of mechanical shock was lower in type I glass vials than in cyclic olefin polymer (COP) vials or in SiOPlasTM COP vials and correlated with the surface roughness of the different vials. To reduce the incidence of cavitation and the adsorption of mAb on glass-water and silicone oil-water interfaces and thus minimize protein damage due to cavitation, PS20, a common nonionic surfactant, was added to formulations. Addition of PS20 to formulations in glass and silicone oil-coated glass vials significantly reduced both incidence of mechanical shock-induced cavitation, and the particle formation that resulted from cavitation events.