Briefly, according to the summary product characteristics, the thawed vaccine was diluted in its original vial with 1.8 mL sodium chloride 9 mg/mL (0.9%) solution for injection, using a 21 gauge or narrower needle and aseptic techniques. After dilution, the vial contains 2.25 mL. Using low dead-volume syringes and/or needles (0.5 mm x 25 mm needles combined with syringe (HUNAN22012021, Hunan Pingan Medical Device Technology) having dead-volume less than 35 microlitres) to extract doses from a single vial, six syringes can be withdrawn with 0.3 mL. This protocol was considered as reference protocol (protocol P1) to compare the use of standard medical devices presenting higher dead-volume in the vaccine extraction and administration.
Depending on body shape, different uncrimped medical devices were tested to administer vaccine: tuberculin syringes of 1.0 mL (ref. 002022140, Penta®) combined to needles for intramuscular administration of 0.5 mm x 25 mm (25 gauges, ref. 402558, Smiths Medical®) or 0.6 mm x 30 mm (23 gauges, ref. 402558, Smiths Medical®). Using these devices, different volumes and techniques of extraction were tested.
As recommended by the drug information, single vial was used to extract six doses (one vial per protocol). Vaccine solution was diluted by 1.8 mL sodium chloride 9 mg/mL (0.9 %) solution using 3 mL syringe (307727, Becton Dickinson France®) combined with a 0.8 mm x 38 mm needle (21 gauges, ref. 402115, Smiths Medical®). The 3 mL syringe was then disconnected and tuberculin syringes withdrawn with 0.30 mL (protocol P2) or 0.35 mL (protocol P3) one after the other using the same 0.8 mm x 38 mm needle. The filled syringes were then connected to 0.5 mm x 25 mm or 0.6 mm x 30 mm needle for administration.
In order to facilitate the extraction of the sixth dose, an alternative strategy of vaccine dose preparation with an air bubble was explored. The air bubble was used to flush the vaccine solution from the dead space of the system to limit lost of vaccine. The vial is taken from a work surface with a 0.8 mm x 38 mm needle to withdraw the vaccine from the bottom of the vial. An air bubble from 0.9 mL corresponding to the dead volume of the system was formed near the plunger of the syringe. On contrary to the current practices, this air bubble was preserved in the syringe and the vaccine solution was withdrawn at different volumes: 0.30 mL (protocol P4), 0.27 (protocols P5 and P6) and 0.25 mL (protocol P7 and P8).
For each protocol tested, empty vials of Comirnaty® of vaccine which were pre-filled in by 0.45 mL of 0.9% sodium chloride solution (Freeflex, Fresenius Kabi France®) to mimic vaccine solution, were used. Each solution was then diluted by 1.8 mL of 0.9% of chloride sodium solution (n=8, CV = 0.96%) according to drug information. Using aseptic technique, vaccine doses defined by the protocol were withdrawn of the vial. If the amount of vaccine remaining in vial cannot provide a full dose, the vial was discarded.
After syringes preparation, vaccine administration was miming for each syringe. The injected volume (repeatability and trueness) was evaluated by weighing after correction by the bulk density of 0.9% sodium chloride solution. The protocol 1 corresponding to Comirnaty® drug information was considered as the reference to compare other protocols.