Methods for manufacturing non-glass prefilled syringes
A method of sterilizing a prefilled syringe comprises assembling a syringe assembly and performing at least one ethylene oxide (EtO) sterilization procedure cycle. The assembling step includes inserting a tip cap at a first end of a plunger, filling a non-glass barrel with sterilization sensitive material at a second end of the barrel, and inserting the plunger into the barrel at a second end to seal the sterilization sensitive material within the barrel. The EtO sterilization procedure cycle comprises undergoing a preprocessing stage, a wash and conditioning stage, an EtO sterilization stage and a wash and post exposure stage. Upon completing the EtO sterilization procedure cycle, a resultant pH of the sterilization-sensitive material does not exceed an acceptable pH range as defined by the United States Pharmacopeia. The disclosure also discusses inserting an assembled prefilled syringe into a procedure tray prior to performing the EtO sterilization procedure cycle.
1 . A method of EtO sterilizing a prefilled syringe, comprising:
providing a syringe prefilled with a sterilization-sensitive solution, the sterilization-sensitive solution being adversely affected when exposed to ethylene oxide (EtO) and having an initial solution pH range of 4.5-7.0;
placing the prefilled syringe into an EtO sterilizable packaging with at least one other medical equipment;
sealing the EtO sterilizable packaging with the prefilled syringe and the at least one other medical equipment therein, before performing an EtO sterilization procedure cycle;
performing the EtO sterilization procedure cycle on the EtO sterilizable packaging including the prefilled syringe and the at least one other medical equipment, the EtO sterilization procedure cycle including a preprocessing stage to initiate growth of microorganisms on an exterior of the prefilled syringe and a wash and conditioning stage to remove air from a treatment chamber containing the packaging including the prefilled syringe and the at least one other medical equipment therein, wherein the wash and conditioning stage includes raising a temperature of the treatment chamber to a conditioning temperature within a range of 85-130° F.; and
initiating an EtO sterilization stage of the EtO sterilization procedure cycle on the EtO sterilizable packaging including the prefilled syringe and the at least one other medical equipment therein within the treatment chamber to sterilize an exterior surface of the prefilled syringe; and
wherein upon completing the EtO sterilization procedure cycle, a resultant pH of the sterilization-sensitive solution remains within the initial solution pH range of 4.5-7.0.
2 . The method of claim 1 , wherein the EtO sterilizable packaging includes a surgical kit.
3 . The method of claim 1 , wherein the EtO sterilizable packaging includes a procedure tray having the prefilled syringe secured therein.
4 . The method of claim 1 , wherein the EtO sterilizable packaging includes at least one of a surgical instrument, a drug, an antiseptic, and dressing.
5 . The method of claim 1 , wherein the preprocessing stage includes increasing the temperature of the treatment chamber and a humidity of the treatment chamber for at least 6 hours.
6 . The method of claim 1 , wherein a barrel of the syringe is formed of at least one of a cyclic olefin polymer (COP) and a cyclic olefin copolymer (COC).
7 . The method of claim 1 , wherein the sterilization-sensitive solution includes at least one of saline, heparinized saline, and lidocaine.
8 . The method of claim 1 , wherein the sterilization-sensitive solution includes at least one of lidocaine hydrochloride, and heparin.
9 . The method of claim 1 , wherein the sterilization-sensitive solution includes lidocaine hydrochloride and epinephrine.
10 . The method of claim 1 , wherein the wash and conditioning stage includes moving the packaging including the prefilled syringe and the at least one other medical equipment therein to the treatment chamber and sealing the treatment chamber.
11 . The method of claim 1 , further comprising:
initiating an evacuation process simultaneous with raising the temperature to the conditioning temperature; and
performing a leak test for a predetermined time period within a range of 5-60 minutes.
12 . The method of claim 11 , further comprising introducing moisture into the treatment chamber to a target range of 0.5-3.0 inHgA relative humidity to achieve a predetermined dwell pressure, wherein the predetermined dwell pressure is maintained for a dwell time within a range of 15-120 minutes.
13 . The method of claim 12 , further comprising injecting Nitrogen gas under pressure into the treatment chamber.
14 . The method of claim 13 , wherein the Nitrogen gas is injected up to 30.5 inHgA.
15 . The method of claim 14 , further comprising evacuating the treatment chamber by subjecting the treatment chamber to a pressure set point within a range of 1-24 inHgA.
16 . The method of claim 1 , wherein upon completing the EtO sterilization procedure cycle, residual ethylene oxide and ethylene chlorohydrin levels in the sterilization-sensitive solution do not exceed 10 ppm.
17 . The method of claim 1 , wherein residual ethylene glycol level in the sterilization-sensitive solution does not exceed 20 ppm.