Prefilled Syringe EO Sterilization With Permeation-Controlled Seals
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Solution Overview
Problem
Existing methods for preparing prefilled syringes face challenges in achieving complete and efficient first and second external surface sterilization while maintaining the sterility of the syringe barrel's interior, particularly for ophthalmic applications where high contamination standards are required.
Innovation Solution
A method involving two sterilization steps using ethylene oxide (EO) at different conditions for the syringe barrel assembly, with the first sterilization allowing EO to permeate through the rubber element and the second preventing its entry into the barrel interior, using rubber materials with controlled gas permeability to ensure tight sealing and sterility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the syringe barrel assembly is sterilized by exposing to ethylene oxide to achieve complete sterilization, then sterilization effectiveness is improved, but ethylene oxide may permeate through the rubber element and contaminate the drug substance
Solution Approach 1:
The rubber element is pre-assembled on the syringe barrel tip before sterilization, creating a barrier structure in advance that prevents EO permeation during the sterilization process
Solution Approach 2:
The rubber element acts as an intermediary barrier between the ethylene oxide sterilization environment and the drug substance, selectively preventing EO permeation while allowing the sterilization process to proceed
2Object-affected harmful factors
If the rubber element is made tightly sealing to prevent EO permeation, then drug substance protection is improved, but sterilization completeness may be compromised
Solution Approach 1:
The rubber element is positioned at a specific location (syringe barrel tip) where it provides localized sealing properties, allowing different regions of the assembly to have different functional characteristics during sterilization
3Reliability
If aseptic filling is performed in class A cleanrooms to maintain sterility, then sterility standard is improved, but manufacturing complexity and cost increase
Solution Approach 1:
The syringe barrel assembly is pre-sterilized by EO exposure before filling, establishing sterility in advance and allowing subsequent filling to be performed in less stringent cleanroom conditions
Solution Approach 2:
The manufacturing process is divided into distinct stages: pre-sterilization of the barrel assembly, then filling operation, where the sterilization function is separated from the filling operation to reduce overall process complexity
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The method results in a prefilled syringe with a tightly sealed and sterile interior, meeting high sterility standards for ophthalmic use by effectively sterilizing the external surfaces without compromising the drug quality.
Implementation Method 1
the rubber element of the needle adaptor cap and the tip of the syringe barrel allowing ethylene oxide to permeate through
Implementation Method 2
the rubber stopper sealing the interior of the syringe barrel and the needle adaptor cap assembled on the tip of the syringe barrel preventing its entry into the barrel interior
Data Source
Figure 1~2
AI summary
A method of preparing a prefilled syringe (1), comprises (i) obtaining a syringe barrel (11) having an open end (111) and a tip (112) with an orifice (113) essentially opposite to the open end (111), and a needle adaptor cap (12) assembled on the tip (112) of the syringe barrel, wherein the needle adaptor cap (12) has a rubber element (121) tightly sealing the orifice (113) of the tip (112) of the syringe barrel (11) and the syringe barrel (11) together with the needle adaptor cap (12) assembled on the tip (112) of the syringe barrel (11) is sterilized by a first sterilizing comprising a main step of exposing the syringe barrel (11) together with the needle adaptor cap (12) assembled on the tip (112) of the syringe barrel (11) to ethylene oxide for about 5 hours to about 60 hours at a relative humidity of about 40% to about 100% and at a temperature of about 30°C to about 60°C; (ii) filling a drug substance (14) through the open end (111) of the syringe barrel (11) into an interior of the syringe barrel; (iii) sealing the interior of the syringe barrel (11) by advancing a rubber stopper (13) through the open end (111) of the syringe barrel (11); (iv) packaging the syringe barrel (11) together with the rubber stopper (13) sealing the interior of the syringe barrel (11) and the needle adaptor cap (12) assembled on the tip (112) of the syringe barrel (11); and (v) second external surface sterilizing the packaged syringe barrel (11) together with the rubber stopper (13) sealing the interior of the syringe barrel (11) and the needle adaptor cap (12) assembled on the tip (112) of the syringe barrel (11). The rubber element (121) of the needle adaptor cap (12) and the rubber stopper (13) are made of a rubber material having a comparably low oxygen transmission rate such as, at 1 atmosphere, of not more than 64 cubic centimeter per square meter and day. The second external surface sterilizing comprises a main step of exposing the packaged syringe barrel (11) together with the rubber stopper (13) sealing the interior of the syringe barrel (11) and the needle adaptor cap (12) assembled on the tip (112) of the syringe barrel (11) to ethylene oxide for about 3 hours to about 30 hours at a relative humidity of about 40% to about 100% and at a temperature of about 25°C to about 45°C. At least one of the duration, the relative humidity and the temperature of the second external surface sterilizing is essentially 28 lower than the respective duration, relative humidity or temperature of the first sterilization.