ABSTRACT
The recent emergence of new drug technologies such as mRNA-based (messenger ribonucleic acid) vaccines developed to fight the outbreak of the Corona Virus Disease (COVID-19) global pandemic has driven increased demand for delivery solutions capable of withstanding deep cold storage conditions down to -50°C, and even down to -80°C. While significant data exist for deep cold storage in vials, little evidence is available for pre-filled syringes. Since pre-filled syringes serve as both the storage container and the delivery mechanism, there are additional risks to performance that must be evaluated, such as plunger gliding performance, syringe lubrication, silicone layer stability, and container closure integrity (CCI). In the present study, a comprehensive assessment of functional and physical performances of Pre-Filled Syringes (PFS filled with water) was performed after one or multiple freeze/thaw (F/T) cycles between ambient temperature and various temperature cycles including -40°C, -50°C or -80°C for both 'staked needle' and 'luer lock' configurations. The experiments were guided by historical normative methods such as ISO11040-4 and USP<1207> and combined with headspace gas analysis for barrel-stopper tightness testing. In addition, they were complemented with a novel approach namely in situ real time optical imagery to track plunger stopper movement during F/T cycle. The findings indicate that there is no significant impact on the functional performances from F/T down to -80°C, while no CCI risk was found after F/T down to -50°C.