Dr. Peer Schrader, Inge Burger, Dr. Florian Maurer, Dr. Alexander Traxl, Jens Herrmann, Dr. Uwe Rothhaar
Having a primary packaging container that serves both as a sterile storage compartment and delivery device to administer drugs is the major driving force for the injectable combination products using prefillable syringes in a variety of applications. However, when it comes to the functional compatibility and delivery reliability between the syringe components (e.g., plunger, barrel, or closure cap) and the drug formulation, these benefits present more challenges than the traditionally used two-unit delivery systems vial and disposable syringe. Especially important properties like the gliding forces of the plunger or the flange strength need to be ensured over the entire shelf life. ISO 11040-4 defines a range of standardised test methods for prefillable glass syringes for the harmonisation of reliability within the industry. In this study, functional and strength tests according to the standards of ISO 11040-4 are performed, namely tests on flange breakage resistance, Luer-cone breakage resistance, needle pull-out force, gliding force, and pull-off force of closure caps. The results are statistically evaluated, thoroughly discussed, and the implications of the results for quality control are highlighted.
The percentage of prefillable syringes used for drug delivery yearly is steadily increasing in the pharmaceutical industry. Beginning with prefillable syringes, the pharmaceutical company/contract filling company is spared the responsibility for the washing, siliconisation, and sterilisation process. In addition, the packaging configurations for prefillable syringes (tubs and nests) are also suitable and relevant for smaller filling batches during small production campaigns. The subsequent versatility makes prefillable syringes suited for many pharmaceutical applications and encourages their increasing use.
To ensure patient safety, having a clear understanding of the behaviour of prefillable syringes in practical use is imperative. Therefore, ISO 11040-41 offers a wide range of test methods meant to give the interested party (i.e. primary packaging engineer tasked with selecting between syringes from different companies; quality control tasked with troubleshooting production and/or field issues) insight into the most essential properties of prefillable syringes. Most of the described tests serve as reference methods to provide a measure for functionality, strength, and quality control in general during production. The same applies to ISO 11040-6,2 which stipulates test methods for the testing of prefillable polymer syringes that are based on methods as per ISO 11040-4.1 Intended for the manufacturers of prefillable syringes, it is making it mandatory to investigate whether the prefillable syringes will withstand the loads exhibited during filling, transportation, or the use in medical practice by medical staff or patients.
The present study gives an overview of the different tests applied on 1 ml long glass syringes. This includes the procedures for flange breakage, Luer-cone breakage, needle pull-out force, gliding force measurements, and the pull-off force of closure caps. For each of the aforementioned methods, 50 specimens are tested, gaining sufficient data to capture their statistical distributions. The experimental methods and the statistical analyses are also discussed regarding their implications for quality control. As an overview, the test methods are briefly introduced in the following:
