Integrity performance assessment of a Closed System Transfer Device syringe adaptor as a terminal closure for Luer-Lock syringes

ABSTRACT Objectives To investigate the container closure integrity of a Closed System Transfer Device syringe adaptor lock in combination with disposable Luer-Lock syringes as the terminal closure device. The United Kingdom (UK) National Health Service (NHS) Pharmaceutical Quality Assurance Committee (PQAC) requires syringe integrity data for final storage devices of aseptic products such as chemotherapy drugs when prepared in advance and stored prior to use as is standard practice for dose banded drugs. The assessment comprised both physical and microbial integrity testing of the combination closed system/ Luer-Lock syringes containers at syringe sizes: 1mL, 20mL, and 50mL. Methods Integrity testing was performed as described in the NHS Pharmaceutical Quality Assurance Committee Yellow Cover Document 2 nd edition 2013 “Protocols for the Integrity Testing of Syringes” with Chemfort™ (Simplivia, IL) syringe adaptor lock (SAL) devices as replacement for sterile blind hubs. Microbiological integrity was assessed according to Method 1 part 1.4 using Brevundimonas diminuta at 32°C for up to 14-days contact time. Two positive control devices per syringe size were tested using a blind hub cap as closure which was loosened prior to test. Physical integrity was assessed using Method 3 of the yellow cover document which is a dye intrusion method. Dye intrusion was assessed both visually and using a validated ultraviolet-visible spectrophotometer method. For each size/ batch of test articles a positive control device (n=1) was assessed using a wire wrapped around the syringe plunger tip deliberately compromising integrity. Negative controls for each size (n=1) consisted of devices not immersed in methylene blue dye. Results Chemfort™ syringe adaptor lock/ Luer-Lock syringe combinations were shown to be: (1) free of microbiological contamination after 14-days contact time (n=60), (2) free of dye intrusion at all syringe sizes tested (n=61 in total). The data demonstrates 100% closure integrity of the final container system when Chemfort™ syringe adaptor lock replaces the syringe hub as the terminal closure device. All positive control devices demonstrated system suitability as container integrity was compromised in all positive control tests. All negative controls were negative for microbial and dye intrusion. Conclusions Syringe adaptor lock components complied with the NHS Pharmaceutical Quality Assurance Committee Yellow Cover Document syringe integrity requirements when used as the terminal closure of Luer-Lock disposable syringes from 1mL up to 50mL. Therefore, syringe adaptor lock (Chemfort™) can be used as the terminal closure system for pre-filled syringes of chemotherapeutic drug products prepared in advance in UK NHS Pharmaceutical Technical Services. What this paper adds What is already known on this subject There is a paucity of data to support the use of closed system transfer device (CSTD) components as terminal closure devices in combination with single use leur-lock syringes in pharmaceutical technical services in the UK. A recent publication in 2020 by Marler-Hausen et al . demonstrated reduction in contamination on a UK hospital day ward when a Chemfort™ syringe adaptor CSTD components were used, providing better protection for healthworkers. National Health Service (NHS) Quality Assurance Committee Yellow Cover Document (YCD) for “Protocols for the Integrity Testing of Syringes” states container integrity data is required to support use of CSTD syringe caps in aseptic services and enabling their greater use in administration. What this study adds This study provides the necessary integrity data for Chemfort™ (Simplivia, IL) syringe adaptor lock components in combination with syringe. Physical and microbiological integrity complied with NHS YCD requirements. Chemfort™ is the first CSTD to meet the YCD acceptance criteria allowing components to be used in aseptic services including Dose-Banding in the UK.