Methods for manufacturing non-glass prefilled syringes

Abstract

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:
 assembling a syringe assembly including:
 inserting the plunger into the barrel at a second end to define a chamber therein; 
 filling a non-glass barrel with sterilization sensitive material at a first end of the barrel; 
 inserting a tip cap at a first end of a barrel to seal the sterilization sensitive material within the barrel; 
 and 
   performing at least one ethylene oxide (EtO) sterilization procedure cycle of the assembled syringe assembly, wherein the sterilization procedure cycle comprises undergoing a preprocessing stage, a wash and conditioning stage, an EtO sterilization stage and a wash and post exposure process, wherein upon completing the EtO sterilization procedure cycle, a resultant pH of the sterilization-sensitive material is within an acceptable pH range as defined by the United States Pharmacopeia.   
     
     
         2 . The method of  claim 1 , wherein the barrel is formed of at least one of a cyclic olefin polymer (COP) and a cyclic olefin copolymer (COC). 
     
     
         3 . The method of  claim 1 , wherein the sterilization sensitive material is introduced into the barrel in an aseptic environment. 
     
     
         4 . The method of  claim 1 , wherein the prefilled syringe assembly is autoclaved prior to undergoing the EtO sterilization procedure cycle. 
     
     
         5 . The method of  claim 1 , wherein the prefilled syringe assembly is subjected to a UV light sterilization process prior to undergoing the EtO sterilization procedure cycle. 
     
     
         6 . The method of  claim 1 , wherein the sterilization sensitive material is one of saline, heparinized saline and lidocaine. 
     
     
         7 . The method of  claim 6 , wherein the acceptable pH range is between 4.5-7.0. 
     
     
         8 . The method of  claim 6 , wherein the acceptable pH range is between 5.0-7.0. 
     
     
         9 . The method of  claim 6 , wherein the acceptable pH range is between 3.5-5.5. 
     
     
         10 . The method of  claim 1 , wherein a stopper is assembled to the plunger before introduction into the barrel, the stopper being manufactured of either bromobutyl or chlorobutyl rubber. 
     
     
         11 . The method of  claim 1 , wherein the preprocessing stage further comprises raising the temperature and humidity of a preconditioning area into which the syringe is located to a predetermined level to initiate growth of microorganisms. 
     
     
         12 . The method of  claim 11 , wherein the temperature is within the range of 90-130° F. 
     
     
         13 . The method of  claim 11 , wherein the humidity is within the range of 45-95%. 
     
     
         14 . The method of  claim 11 , wherein a dwell time for maintaining the predetermined level of the temperature and humidity is within the range of 6-96 hours. 
     
     
         15 . The method of  claim 11  wherein the preconditioning area is also a sterilization area where the EtO sterilization stage. 
     
     
         16 . The method of  claim 15 , wherein the preconditioning area is also an aeration area. 
     
     
         17 . The method of  claim 1 , wherein the wash and conditioning stage includes moving the syringe to a sterilization chamber, sealing the chamber and raising the temperature to a conditioning temperature within a range of 85-130° F. 
     
     
         18 . The method of  claim 1 , wherein the wash and conditioning stage includes raising the temperature to a conditioning temperature within the range of 85-130° F. 
     
     
         19 . The method of  claim 18 , further comprising initiating an evacuation process simultaneous with raising the temperature to the conditioning temperature. 
     
     
         20 . The method of  claim 19 , wherein the evacuation process applies vacuum pressure within a range of 1-24 inHgA. 
     
     
         21 . The method of  claim 19 , wherein the evacuation process applies vacuum pressure to a set point of 10 inHgA, within a tolerance of ±0.5 inHgA. 
     
     
         22 . The method of  claim 19 , further comprising performing a leak test for a predetermined time period within the range of 5-60 minutes. 
     
     
         23 . The method of  claim 22 , further comprising introducing moisture into a sterilization chamber to a target range of 0.5-3.0 inHgA relative humidity to achieve a predetermined dwell pressure. 
     
     
         24 . The method of  claim 23 , wherein the predetermined dwell pressure is within the range of 2.3-14 inHgA. 
     
     
         25 . The method of  claim 24 , wherein the dwell pressure is maintained for a dwell time within the range of 15-120 minutes. 
     
     
         26 . The method of  claim 23 , further comprising injecting Nitrogen gas under pressure into the sterilization chamber. 
     
     
         27 . The method of  claim 26 , wherein the Nitrogen gas is injected up to 30.5 inHgA. 
     
     
         28 . The method of  claim 27 , wherein the sterilization chamber is evacuated by subjecting the sterilization chamber to a pressure set point within the range of 1-24 inHgA. 
     
     
         29 . The method of  claim 28 , wherein the injection of Nitrogen gas and the evacuation of the sterilization chamber is repeated up to four times. 
     
     
         30 . The method of  claim 28 , further comprising introducing moisture into the serialization chamber to a target range of 0.5-30 inHgA to achieve a predetermined dwell pressure. 
     
     
         31 . The method of  claim 30 , wherein the predetermined dwell pressure is within the range of 2.3-14.0 inHgA. 
     
     
         32 . The method of  claim 31 , wherein the dwell pressure is maintained for a dwell time within the range of 15-120 minutes. 
     
     
         33 . The method of  claim 1 , wherein the EtO sterilization stage further comprises introducing EtO gas into a chamber containing the syringe until reaching a predetermined pressure level. 
     
     
         34 . The method of  claim 33 , wherein the predetermined pressure level is within the range of 10.7-29.9 inHgA. 
     
     
         35 . The method of  claim 34 , wherein a concentration level of EtO within the sterilization chamber is measured to verify that the EtO concentration level is within a target range of 150-800 mg/L. 
     
     
         36 . The method of  claim 34 , further comprising introducing a nitrogen blanket in the sterilization chamber to a target range. 
     
     
         37 . The method of  claim 36 , wherein the target range is up to 30 inHgA. 
     
     
         38 . The method of  claim 35 , wherein the EtO concentration level is maintained at a predetermined dwell temperature for a predetermined dwell time period. 
     
     
         39 . The method of  claim 38 , wherein the predetermined dwell temperature is within the range of 102-140° F. and the predetermined dwell time period is within the range of 1-24 hours. 
     
     
         40 . The method of  claim 39 , further comprising introduction of additional EtO to reach the EtO concentration level if the EtO concentration level falls outside the target range of 150-800 mg/L. 
     
     
         41 . The method of  claim 1 , wherein the wash and post exposure stage further comprises evacuating EtO gas and Nitrogen introduced during the EtO sterilization stage by application of vacuum pressure. 
     
     
         42 . The method of  claim 41 , wherein the vacuum pressure is applied within the range of 1-24 inHgA. 
     
     
         43 . The method of  claim 42 , wherein the vacuum pressure is applied within the range of 1 to 30 minutes. 
     
     
         44 . The method of  claim 43 , further comprising injecting Nitrogen gas into a sterilization chamber containing the syringes under pressure up to 30.5 inHgA. 
     
     
         45 . The method of  claim 44 , wherein the process of injecting Nitrogen gas into the sterilization chamber is repeated up to 4 times. 
     
     
         46 . The method of  claim 45 , further comprising evacuating the sterilization chamber to a pressure within the range of 1-24 inHgA. 
     
     
         47 . The method of  claim 46 , further comprising initiating an air wash of the sterilization chamber. 
     
     
         48 . The method of  claim 47 , wherein the air wash further comprises injecting air under pressure up to 30.5 inHgA. 
     
     
         49 . The method of  claim 48 , further comprising repeating the air wash of the sterilization chamber up to four times. 
     
     
         50 . The method of  claim 49 , further comprising aerating the sterilization chamber within the range of 24-120 hours. 
     
     
         51 . The method of  claim 1 , further comprising placing the assembled syringe assembly into an EtO serializable packaging with other surgical equipment, sealing the EtO serializable packaging with the assembled syringe assembly and the other surgical equipment therein, before performing the EtO sterilization procedure cycle. 
     
     
         52 . The method of  claim 1 , wherein upon completing the EtO sterilization procedure cycle, the residual ethylene oxide and ethylene chlorohydrin levels in the sterilization sensitive material shall not exceed 10 ppm. 
     
     
         53 . The method of  claim 1 , wherein the residual ethylene glycol level in the sterilization sensitive material shall not exceed 20 ppm. 
     
     
         54 . The method of  claim 1 , wherein the syringe is subjected to multiple EtO sterilization procedure cycles. 
     
     
         55 . A method of sterilizing a surgical kit containing a prefilled syringe, comprising:
 inserting a syringe that is prefilled with sterilization sensitive material disposed within a non-glass barrel into a procedure tray with other surgical equipment;   sealing the procedure tray with the syringe that is prefilled with sterilization sensitive material and other surgical equipment therein;   performing at least one ethylene oxide (EtO) sterilization procedure cycle of the sealed procedure tray, wherein the sterilization procedure comprises undergoing a preprocessing stage, a wash and conditioning stage, an EtO sterilization stage and a Wash and post exposure stage, wherein upon completing the EtO sterilization procedure cycle, a resultant pH of the sterilization-sensitive material is within an acceptable pH range as defined by the United States Pharmacopeia.   
     
     
         56 . The method of sterilizing a surgical kit of  claim 52 , wherein the syringe that is prefilled with sterilization sensitive material is autoclaved prior to undergoing the EtO sterilization procedure cycle. 
     
     
         57 . A method of sterilizing a prefilled container, comprising:
 filling a container constructed of at least one of a cyclic olefin polymer (COP) and a cyclic olefin copolymer (COC) with sterilization sensitive material;   sealing the container to create a barrier for the sterilization sensitive material; and   performing at least one ethylene oxide (EtO) sterilization procedure cycle of the sealed container, wherein the sterilization procedure comprises undergoing a preprocessing stage, a wash and conditioning stage, an EtO sterilization stage and a wash and post exposure stage, wherein upon completing the EtO sterilization procedure cycle, a resultant pH of the sterilization-sensitive material is within an acceptable pH range as defined by the United States Pharmacopeia.   
     
     
         58 . A method of sterilization a prefilled container, comprising:
 assembling a syringe assembly including:
 inserting the plunger into the barrel at a second end to define a chamber therein; 
 filling a non-glass barrel with sterilization sensitive material at a first end of the barrel; 
 inserting a tip cap at a first end of a barrel to seal the sterilization sensitive material within the barrel; 
 and 
   performing at least one ethylene oxide (EtO) sterilization procedure cycle of the assembled syringe assembly, wherein the sterilization procedure cycle comprises undergoing a preprocessing stage, a wash and conditioning stage, an EtO sterilization stage and a wash and post exposure process, wherein upon completing the EtO sterilization procedure cycle, a resultant residual of Ethylene Oxide gas and Ethylene Chlorohydrine gas in the sterilization-sensitive material does not exceed 10 ppm.