(T1230-01-03) Break Loose Force and Glide Force Evaluation of Various Container Closure System Combination for Empty Syringe

Purpose: To conduct a comprehensive evaluation of break loose force and glide force (BLGF) on 1 ml long(L) and 2.25 ml empty prefilled syringes (PFSs) for biologics from three vendors in combination with 4-5 types of plunger stoppers from four vendors. To assess fifteen container closure system (CCS) combinations for the 1 mL L syringes and the 2.25 mL syringes, respectively. To investigate potential factors that might impact BLGF, including key dimensional analysis of the syringes and plunger stoppers and the measurement of silicone oil content and distribution within the syringes. To evaluate the impact of the properties of the plunger stoppers, such as design, formulation, and manufacturing process, on the BLGF performance.

Methods: BLGF Test - A material testing machine (Instron:2344) with fitting accessories was applied to perform the BLGF test. The parameter setting includes 100N load cell, 200 mm/min crosshead speed, 65 Hz data acquisition frequency, 0.2N preload, 20 mm/min preload crosshead velocity, 30N end-of-test criteria. Stoppers were preset in empty syringes at least 12 hours before testing. The depth of the stoppers was determined based on the stopper position for 1 mL water in a 1 mL L syringe and 1.7 mL water in a 2.25 mL syringe. Additionally, the plunger stopper insertion depth (PSID) was set at approximately 11–12 mm for 1 mL L syringes and 12–13 mm for 2.25 mL syringes. Plunger rods were inserted at least 30 minutes before testing. Samples were placed under testing conditions (23℃ ± 5℃ temperature and 50% ± 25% humidity) for at least 30 minutes before testing. Silicone Oil Measurement - The evaluation of silicone oil content and distribution in 1 mL L and 2.25 mL syringes was conducted using Bouncer (Unchained). The test was performed in binary (BI) mode. The instrument captured measurements at 30-degree intervals, collecting data across up to 12 lines in total. Key Dimension Measurement - Inner diameter of syringe and maximum diameter of plunger stopper were measured with an image dimension measurement system.

Results: BLGF Test Results of 1 mL L PFS CCS - For each type of plunger stopper, BLGF performance among the three syringes is consistent. For plunger stoppers with the same design, formulation, and coating, BLGF performance of plunger stopper B was slightly better than the other two plunger stoppers (A and C) in each syringe group with lower variation. The differences among the three stoppers are the washing process, siliconization process, sterilization method, and package. Plunger stopper E showed the best BLGF performance, with plunger stopper D coming in second. BLGF Test Results for 2.25 mL PFS CCS - For each type of plunger stopper, BLGF performance is consistent among the three syringes. For plunger stoppers with same design, formulation, and coating, BLGF performance of plunger stopper C was the best, while the one of A was the worst. The differences among the three stoppers are the washing process, siliconization process, sterilization method, and package. Plunger stopper E showed the best BLGF performance, with plunger stopper D achieving second. Silicone Oil Measurement - Silicone oil content of the 1 ml L syringe Z and 2.25 mL syringe X was the lowest in each group, which might be attributed to the longer time elapsed since manufacture. Although the silicone oil content varied between syringes, the difference had little impact on BLGF performance among the three syringes with the same plunger stopper. Key Dimension Measurement - The three syringes had a similar inner diameter, and the difference was within 0.1 mm. Plunger stopper E had the largest maximum outer diameter, but the difference among the plunger stoppers was also within 0.1 mm.

Conclusion: For the same plunger stopper, the syringes from the three vendors showed little impact on BLGF performance. In addition, the variation of silicone oil content in the syringes did not affect BLGF performance. For each syringe group, BLGF performance varied obviously among the plunger stoppers. The differences in design, formulation, and manufacturing processes might play a dominant role in BLGF performance.