3PC-006 Switching to silicone oil-free syringes for intravitreal application: design of a regulatory compliant container closure integrity test realisable in a hospital pharmacy
Year: 2025
Type: conference-paper
Abstract: Background and Importance Our hospital pharmacy compounds medicinal products for intravitreal application into ready-to-use syringes. The commonly used lubricant silicone oil has been shown in studies, since over 15 years, to elicit adverse reactions like floaters, inflammatory reactions and rapid intraocular pressure spikes. Silicone oil-free alternatives, with minimal dead space, have only recently been available and are currently a hot topic for hospital use. Before using them in production, all primary packaging containers in aseptic processes must be checked for closure integrity. Aim and Objectives This study describes the design of a container closure integrity test (CCIT) according to regulatory guidelines EU GMP Annex 1 using resources available to our hospital pharmacy. All silicone oil-free syringes that were locally available and suitable for intravitreal application were investigated. Three products met these conditions and were tested as stopper capped systems (i.e. no needle attached). Material and Methods Applicable guidelines do not provide precise experimental detail on how the CCIT should be executed, rather the manufacturer needs to design and validate an experiment. EU GMP Annex 1 8.23 and 8.25 demand validated methods, that include environmental parameters which can negatively impact packaging integrity (i.e. decompression during transport). A dye ingress test under complete submersion and reduced pressure with UV-Vis quantification and visual readout was designed. Results All syringe systems tested passed the integrity test and all artificially created positive controls showed a strong signal. The limit of detection using methylene blue dye was 1.7 ng/mL. The two different syringe tip closure types, luer lock (threaded sleeve fitting) and luer slip (tapered friction fitting, without threads) showed no difference. Conclusion and Relevance All syringes used oleamide as the lubrication agent mixed into the polypropylene barrel material and passed testing. The devices needed for CCIT were kept economical and broadly available to enable hospital pharmacies with limited budget to design a GMP compliant CCIT. The designed test is not applicable for on-line testing but rather meant for validation off-line on representative syringe samples. Summarising, the CCIT described in this work requires roughly two hours start to finish but can be executed with minimal prerequisites at low cost compared to other methods used in industrial settings. References and/or Acknowledgements Conflict of Interest No conflict of interest
Author: S Decker
Language: English
Subfield: Analytical Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
OpenAlex ID: W4408376858