Comparing Container Closure Integrity Test Methods - Performance of Headspace Carbon Dioxide Analysis versus Helium Leakage Using Positive Controls.

As described in USP Chapter <1207>, the deterministic leak test methods using laser-based gas headspace analysis and helium leakage are those with the highest sensitivities. As stated in the chapter, ″no single package leak test or package seal quality test method is applicable to all product-package systems″; therefore, knowing the advantages and disadvantages of both of these techniques, and the extent to which they can be substituted for each other, is valuable. In an effort to begin addressing this issue, a systematic study using these two techniques has been performed. This study used the same well-defined positive controls prepared with microcapillaries for both measurement techniques. For the headspace gas analysis technique, the headspace carbon dioxide content was measured at multiple timepoints during three separate conditioning cycles using either a 0.5, 1.0, or 2.0 bar CO2 overpressure; the observed change in headspace carbon dioxide was then used to determine an ingress rate for each positive control. For the helium leakage technique, the positive controls were measured with a standard helium leak detector with 100% helium atmosphere on the atmospheric pressure side of the artificial defects. The resulting leakage rates from both techniques were compared for ingress into both ISO 2R and ISO 10R vials. The obtained correlation between helium and carbon dioxide leakage rates resulted in a minimum R2 coefficient of 0.98 across all 12 runs. Additionally, both setups met the acceptance criteria for accuracy with their respective calibrated standards.

Method Comparison Study-One Step Forward toward Robust Silicone Layer Thickness Measurements.

In the past decades, the silicone layer thickness and its distribution on the inner glass barrels of prefilled syringes have been characterized in several studies. However, the limited number of adequate methods to characterize thin baked-on silicone layers and the destructive nature of some analytical techniques suggest challenges to the inter-lab reproducibility of some methods. In this study, the measured silicone layer thickness of baked-on siliconized syringes was compared between two laboratories, both equipped with white light reflectometry coupled to laser interferometry instrumentation (Bouncer, LE UT 1.0, LE UT 2.0). The quantity of silicone oil of a subset of those syringes was measured by Fourier transform infrared spectroscopy. Glide force tests were realized as complementary measurements on both syringes analyzed by white light reflectometry coupled to laser interferometry instrumentation and on non-analyzed identical syringes from the same lot. Silicone profiles of all prefilled syringes including the limit of detection results replaced with 20 nm were comparable, but values were slightly lower when measured with the Bouncer instrument. An increase of the layer thickness from the finger flange to the needle side was found for all syringes with all instruments (20 nm to 130-140 nm). Glide force results were similar except for a difference in peak width in the break loose region between the laboratories. The mean quantities of silicone oil found by both laboratories were similar (64 µg/syringe and 69 µg/syringe). Overall, comparable results between laboratories suggest a good reproducibility of the thickness measurement method as a result of thorough method understanding and defining key method parameters. Hence this study presents a robust inter-lab comparison between silicone layer thickness measurements that has been a lack in the literature up to now.