The tip cap comparability study resulted in one tip cap material having superior compatibility among the three that were tested. to select the optimum closure materials as well as the correct syringe processing method. Results indicate that the model mAb formulation used was sensitive to high levels of silicone oil especially under accelerated temperature conditions resulting in formation of proteinCsilicone particles in the solution for samples that were spiked with the silicone oil. Agitation stress did not have any significant impact on the quality attributes tested. Samples stored in syringe barrels that were processed with sprayed-on silicone had higher levels of CPDA subvisible particles as compared to those that were processed with the baked-on process. The tip cap comparability study resulted in one tip cap material having superior compatibility among the three that were tested. The quality attribute that was most impacted by the tip cap CPDA materials was mAb oxidation. An approach for evaluation of primary packaging components during the development of pre-filled syringe presentations for biotechnology-based compounds CPDA has been highlighted. investigated the propensity of model proteins to aggregate in the presence of Si-oil and found that all the proteins tested aggregated in the presence of 0.5% Si-oil irrespective of molecular weight and isoelectric point of the protein (7). Thirumangalathu studied Si-oil induced aggregation of an IgG1 monoclonal antibody as a function of agitation, temperature, pH, ionic strength, and excipient levels such as polysorbate 20 and sucrose. Although agitation-induced aggregation was observed at higher speeds, addition of polysorbate 20 inhibited the aggregate formation (8). Overcashier described some technical considerations for development of protein therapeutics STAT91 in PFS including selection of primary components such as plungers and needle shields based on syringe functionality experiments (1). In this paper, we have provided general guidance on the development of biotechnology products in PFS. We have systematically evaluated the effect of Si-oil on the compatibility of a mAb formulation through spiking studies and accelerated temperature stability studies. A study to compare two types of syringe barrels differentiated by the siliconization process has been presented. Furthermore, a strategy for screening primary components has been provided for determining optimum primary components for PFS systems. MATERIALS AND METHODS Materials An in-house IgG2 mAb solution at 5 or 10?mg/mL in a buffer system at pH?6.0 containing surfactant and a disaccharide as excipients was used as a model protein formulation for this study. Si-oil (Dimithicone, 350?cs) was purchased from Dow Corning, Midland, MI, USA. The vials and syringes used in the study were made up of type I glass. Syringes were sourced from CPDA multiple vendors each using different processing methodologies to process and siliconize the barrels. Elastomeric closure components which can be sterilized by autoclaving (plungers) or ETO sterilization (tip caps) were used in this study. These were sourced from multiple vendors and are free of natural rubber and molded from standard formulations that meet requirements of the major pharmacopoeias. Silicone OilCWater Emulsion Preparation A stock solution of silicone oil/water emulsion was prepared as described earlier by Jones (7). Si-oil was added in deionized water in a 50-mL centrifuge tube to obtain Si-oil concentration in water of 30?mg/mL. This solution was sonicated (Misonix S-4000) for approximately 5?min at 50% amplitude to obtain the emulsion which was opalescent due to fine dispersed Si-oil droplets. The stock solution was diluted to obtain emulsions at concentrations of 10 and 20?mg/mL Si-oil in water. The freshly prepared solutions were used to spike Si-oil into the mAb formulations. Agitation and Real-Time Stability Study Setup for the Spiked Samples Type 1 glass vials (2?mL) were filled with 1?mL of the mAb formulation at 10?mg/mL and were spiked with 0.5, 1.0, or 1.5?mg equivalent of Si-oil. A control arm containing vials that were not spiked with Si-oil was included. The vials were placed in a box in the horizontal orientation to CPDA maximize the airCwater interface. The boxes were then placed on orbital shakers at 5C and room temperature and agitated at 300?rpm for 5 and 3?days, respectively. A vial from each group (control, 0.5, 1.0, and 1.5?mg/mL Si-oil) was removed after days?1, 2, and 3 at room temperature and after days?1, 3, and 5 at 5C. In addition to the agitation stress study, a separate real-time and accelerated temperature stability study at 25C and 40C was initiated for vials that were spiked with the various levels of Si-oil. All stability vials were placed in the inverted orientation to maximize contact with the closure as a worse-case scenario. Stability Study Using Pre-filled Syringes Two types of syringes, each with a different processing method, were used. The first type of.