Impact of injection time and protein modality on particle formation when using closed system transfer devices

The impact of injection time, protein modality and concentration/viscosity during the administration of biologics using closed system transfer devices (CSTDs) on drug product quality was investigated. Three brands of CSTDs with different silicone oil levels and fluid path geometries were used to simulate injections through both IV lines and IV bags using two model proteins (a monoclonal antibody [mAb] and an antibody fusion protein). There was an inverse relationship between visible and subvisible particles levels and injection time regardless of the protein modality and CSTD tested. Data from subvisible particle analyses suggested most particles were silicone oil following rapid injection times. Dynamic light scattering detected proteinaceous aggregates that formed following rapid injections of lower concentrations of the antibody fusion protein but not for the mAb. Computational Fluid Dynamics analysis demonstrated that shorter injection times and higher protein concentration/viscosity of the products increased both interfacial and wall shear stresses, and showed that these stresses differed among brands of CSTD when analyzed at the same injection time and viscosity.